bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Pharmacophore Model for SARS-CoV-2 3CLpro Small Molecule Inhibitors and in Vitro Experimental Validation of Computationally Screened Inhibitors
Authors: Glaab Enrico , Manoharan Ganesh Babu , Abankwa Daniel 
Published: March 2021

AbstractAmong the biomedical efforts in response to the current coronavirus (COVID-19) pandemic, pharmacological strategies to reduce viral load in patients with severe forms of the disease are being studied intensively. One of the main drug target proteins proposed so far is the SARS-CoV-2 viral protease 3CLpro (also called Mpro), an essential component for viral replication. Ongoing ligand- and receptor-based computational screening efforts would be facilitated by an improved understanding of the electrostatic, hydrophobic and steric features that characterize small molecule inhibitors binding stably to 3CLpro, as well as by an extended collection of known binders.Here, we present combined virtual screening, molecular dynamics simulation, machine learning andin vitroexperimental validation analyses which have led to the identification of small molecule inhibitors of 3CLpro with micromolar activity, and to a pharmacophore model that describes functional chemical groups associated with the molecular recognition of ligands by the 3CLpro binding pocket. Experimentally validated inhibitors using a ligand activity assay include natural compounds with available prior knowledge on safety and bioavailability properties, such as the natural compound rottlerin (IC50= 37 µM), and synthetic compounds previously not characterized (e.g. compound CID 46897844, IC50= 31 µM). In combination with the developed pharmacophore model, these and other confirmed 3CLpro inhibitors may provide a basis for further similarity-based screening in independent compound databases and structural design optimization efforts, to identify 3CLpro ligands with improved potency and selectivity.Overall, this study suggests that the integration of virtual screening, molecular dynamics simulations and machine learning can facilitate 3CLpro-targeted small molecule screening investigations. Different receptor-, ligand- and machine learning-based screening strategies provided complementary information, helping to increase the number and diversity of identified active compounds. Finally, the resulting pharmacophore model and experimentally validated small molecule inhibitors for 3CLpro provide resources to support follow-up computational screening efforts for this drug target.
A heterohexameric protein consisting of six linked single-domain antibodies is highly protective for BoNT/A, BoNT/B and BoNT/E exposures
Authors: Mukherjee Jean , Tremblay Jacqueline M. , Debatis Michelle , Foss Alexa , Awata Junya , Shoemaker Charles B. 
Published: March 2021

AbstractBotulinum neurotoxin (BoNT) serotypes A, B and E cause the vast majority of human botulism cases and pose the greatest bioterrorism threats. We previously identified multiple camelid single-domain antibodies (VHHs) that each neutralize BoNT/A, BoNT/B or BoNT/E. We also demonstrated that heterodimers of linked toxin-neutralizing VHHs are much more potent than VHH monomer pools in preventing BoNT intoxication. In this study, we expressed two different heterohexamer proteins (VNA1-ABE and VNA2-ABE) of ~100 kDa secreted from mammalian host cells, each containing the same six linked anti-BoNT VHH components ordered in two different combinations. Each heterohexamer contained two VHHs that neutralize BoNT/A, BoNT/B or BoNT/E. Both heterohexameric antitoxins displayed similar strong binding properties for the three targeted BoNT serotypes by ELISA. One ug of each heterohexameric antitoxin fully protected groups of mice co-administered with 100 LD50of BoNT/A, BoNT/B or BoNT/E, or a pool containing 100 LD50of each of the three toxins. The results demonstrate that long chains of at least six different linked VHHs can be expressed such that all component VHHs in the multimer retain their target binding activities. These findings make more feasible the development of a BoNT antitoxin product consisting of a small pool of proteins that, in combination, neutralize all known BoNT serotypes and subtypes.Key ContributionHeteromultimeric proteins consisting of six linked, VHH antibodies, and including VHHs that neutralize BoNT/A, BoNT/B and BoNT/E, retain high potency to protect mice challenged with high doses of all three of these BoNT serotypes.
Re-examining the impact of financial intermediation on economic growth: evidence from Turkey
Authors: Yakubu Ibrahim Nandom , Abokor Aziza Hashi , Gedik Balay Iklim 
Published: March 2021

PurposeThis study seeks to investigate the impact of financial intermediation on economic growth in Turkey using annual data spanning 1970–2017.Design/methodology/approachBased on the results of the augmented Dickey–Fuller and Phillips–Perron unit root tests for stationarity, the authors employ the Autoregressive Distributed Lag (ARDL) bounds testing to cointegration to establish the long-run impact of financial intermediation alongside other control factors on economic growth. The study also examines the short-run relationship between financial intermediation and economic growth by estimating the Error Correction Model (ECM).FindingsThe authors’ findings indicate that financial intermediation significantly influences economic growth in both short and long run. However, the effect is positive only in the short run, lending support to the supply-leading hypothesis. Regarding the control variables, the authors observe that while financial openness shows a positive significant impact on economic growth in the long run, gross fixed capital formation matters only in the short run. The results further infer that regardless of the time period, inflation impedes economic growth.Originality/valueIn the empirical analysis of the relationship between financial intermediation and economic growth, financial intermediation is always measured using a single variable. The authors argue that such studies could produce bias and misleading results given that a single proxy does not adequately reflect financial intermediation activities. Likewise, such findings may delude policy implementation. To provide a more vivid and robust analysis, the authors employ the Principal Component Analysis (PCA) to construct a composite index for financial intermediation based on three broad measures. The researchers’ are unaware of any study on the financial intermediation–economic growth nexus using a composite index of financial intermediation. Thus, this paper fills this lacuna in the literature.
Physico-chemical and mechanical properties of novel electrospun polyurethane composite with enhanced blood compatibility
Authors: Mani Mohan Prasath , Jaganathan Saravana Kumar 
Published: March 2021

Purpose
This study aims to fabricate an electrospun scaffold by combining radish (Ra) and cerium oxide (CeO2) into a polyurethane (PU) matrix through electrospinning and investigate its feasibility for cardiac applications.

Design/methodology/approach
Physicochemical properties were analysed through various characterization techniques such as scanning electron microscopy (SEM), Fourier transforms infrared transforms analysis (FTIR), contact angle measurements, thermal analysis, atomic force microscopy (AFM) and mechanical testing. Further, blood compatibility assessments were carried out through activated partial thromboplastin time (APTT) and prothrombin time (PT) and hemolysis assay to evaluate the anticoagulant nature.

Findings
PU/Ra and PU/Ra/CeO2 exhibited a smaller fibre diameter than PU. Ra and CeO2 were intercalated in the polyurethane matrix which was evidenced in the infrared analysis by hydrogen bond formation. PU/Ra composite exhibited hydrophilic nature whereas PU/Ra/CeO2 composite turned hydrophobic. Surface measurements depicted the lowered surface roughness for the PU/Ra and PU/Ra/CeO2 compared to the pristine PU. PU/Ra and PU/Ra/CeO2 displayed enhanced degradation rates and improved mechanical strength than the pristine PU. The blood compatibility assay showed that the PU/Ra and PU/Ra/CeO2 had delayed blood coagulation times and rendered less toxicity against red blood cells (RBC’s) than PU.

Originality/value
This is the first report on the use of radish/cerium oxide in cardiac applications. The developed composite (PU/Ra and PU/Ra/CeO2) with enhanced mechanical and anticoagulant nature will serve as an indisputable candidate for cardiac tissue regeneration.
Winsome Joy: from educator to entrepreneur
Authors: MacNeil Heatherjean , Wiehe Lopes Amanda , Ozkazanc-Pan Banu , Douglass Anne 
Published: March 2021

Research methodology
The information presented in this case was gathered through interviews and observations carried out during the time Ms Joy attended the Initiative for A Competitive Inner City business support program in 2017. In addition, focus groups that took place after the program provided important information and insights into her decision-making process and business goals. Additional interviews were conducted in 2018 and 2019 after the business program ended to gain in-depth knowledge of Ms Joy’s entrepreneurial journey.

Case overview/synopsis
This case details the experiences of Winsome Joy in recognizing market opportunities in the child care industry and then expanding into the educational materials industry. The case focuses on challenges related to founding and sustaining her business and the ways in which Ms Joy engaged in “opportunity recognition” and “effectuation” to become a successful entrepreneur. The case points out the challenges of the child care and early education field in terms of professional training, hiring practices and retaining qualified staff. It provides an aspirational role model who has overcome these challenges by finding and recognizing new market opportunities.

Complexity academic level
This case is relevant for undergraduate and graduate courses in entrepreneurship.
Body size and environment influence both intraspecific and interspecific variation in daily torpor use across hummingbirds
Authors: Spence Austin R. , Tingley Morgan W. 
Published: March 2021

Abstract

Torpor, or a regulated drop in body temperature and metabolic rate, allows animals to inhabit energetically costly environments, but among torpor‐using species, we have a poor understanding of how plasticity in torpor use relates to the experienced environment.

To better understand the ecology of daily torpor, we completed the largest study to date on the intraspecific variation of daily torpor use in hummingbirds by exposing 149 individuals of two hummingbird species to ambient or experimentally cooled temperatures in a field setting.

The smaller species, a latitudinal migrant, used daily torpor frequently under ambient conditions. The larger species, an elevational migrant, also used daily torpor regularly, but further increased the frequency of daily torpor use when experiencing colder temperatures and prior to migration—indicating a facultative adaptation.

To place our results within a broader phylogenetic context, we combined our experimental results with a meta‐analysis, including 31 species and all major hummingbird clades, and found a broad taxonomic pattern in which smaller hummingbirds are more likely to use daily torpor than their larger counterparts. Smaller hummingbirds may be physiologically constrained, requiring nearly obligate daily torpor use, while larger hummingbirds are physiologically more flexible and can facultatively respond to changing environmental conditions.

Our results reveal how physiological traits, such as the frequency and depth of daily torpor, can provide a mechanism to understand how hummingbird species have established and persisted across broad environmental gradients.

A free Plain Language Summary can be found within the Supporting Information of this article.
Non‐small‐cell lung cancer with ERBB2 mutation in non‐tyrosine kinase domain benefits from pyrotinib: A case report
Authors: Ni Jun , Si Xiao‐yan , Zhang Li 
Published: March 2021

AbstractTyrosine kinase domain (TKD) mutation and particularly exon 20 insertion mutations of erb‐b2 receptor tyrosine kinase 2 (ERBB2/HER2) have been extensively reported in non‐small cell lung cancer (NSCLC). Nevertheless, the clinical significance of non‐TKD mutations remains unknown. To date, no clinical trials have revealed that tyrosine kinase inhibitors are effective in NSCLC patients with non‐TKD ERBB2 mutations. Here we report a patient with advanced lung adenocarcinoma harboring non‐TKD mutation of ERBB2, S335C, without other actionable alterations benefited from pyrotinib. After first‐line treatment of pyrotinib monotherapy, a pan‐HER inhibitor, the patient achieved a durable partial response with good tolerance. This case powerfully illustrates that pyrotinib might be a promising first‐line treatment strategy for NSCLC patients with non‐TKD mutation of ERBB2.
COVID‐19 pandemic and allergen immunotherapy—an EAACI survey
Authors: Pfaar Oliver , Agache Ioana , Bonini Matteo , Brough Helen Annaruth , Chivato Tomás , Del Giacco Stefano R. , Gawlik Radoslaw , Gelincik Aslı , Hoffmann‐Sommergruber Karin , Jutel Marek , Klimek Ludger , Knol Edward F. , Lauerma Antti , Ollert Markus , O’Mahony Liam , Mortz Charlotte G. , Palomares Oscar , Riggioni Carmen , Schwarze Jürgen , Skypala Isabel , Torres María José , Untersmayr Eva , Walusiak‐Skorupa Jolanta , Chaker Adam , Giovannini Mattia , Heffler Enrico , Jensen‐Jarolim Erika , Quecchia Cristina , Sandoval‐Ruballos Mónica , Sahiner Umit , Tomić Spirić Vesna , Alvaro‐Lozano Montserrat 
Published: March 2021

AbstractBackgroundAs in many fields of medical care, the coronavirus disease 2019 (COVID‐19) resulted in an increased uncertainty regarding the safety of allergen immunotherapy (AIT). Therefore, the European Academy of Allergy and Clinical Immunology (EAACI) aimed to analyze the situation in different countries and to systematically collect all information available regarding tolerability and possible amendments in daily practice of sublingual AIT (SLIT), subcutaneous AIT (SCIT) for inhalant allergies and venom AIT.MethodsUnder the framework of the EAACI, a panel of experts in the field of AIT coordinated by the Immunotherapy Interest Group set‐up a web‐based retrospective survey (SurveyMonkey®) including 27 standardized questions on practical and safety aspects on AIT in worldwide clinical routine.Results417 respondents providing AIT to their patients in daily routine answered the survey. For patients (without any current symptoms to suspect COVID‐19), 60% of the respondents informed of not having initiated SCIT (40% venom AIT, 35% SLIT) whereas for the maintenance phase of AIT, SCIT was performed by 75% of the respondents (74% venom AIT, 89% SLIT). No tolerability concern arises from this preliminary analysis. 16 physicians reported having performed AIT despite (early) symptoms of COVID‐19 and/or a positive test result for severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2).ConclusionsThis first international retrospective survey in atopic diseases investigated practical aspects and tolerability of AIT during the COVID‐19 pandemic and gave no concerns regarding reduced tolerability under real‐life circumstances. However, the data indicate an undertreatment of AIT, which may be temporary, but could have a long‐lasting negative impact on the clinical care of allergic patients.
Carbohydrate epitopes currently recognized as targets for IgE antibodies
Authors: Platts‐Mills Thomas A. , Hilger Christiane , Jappe Uta , van Hage Marianne , Gadermaier Gabriele , Spillner Edzard , Lidholm Jonas , Keshavarz Behnam , Aalberse Rob C. , van Ree Ronald , Goodman Richard E. , Pomés Anna 
Published: March 2021

AbstractUntil recently, glycan epitopes have not been documented by the WHO/IUIS Allergen Nomenclature Sub‐Committee. This was in part due to scarce or incomplete information on these oligosaccharides, but also due to the widely held opinion that IgE to these epitopes had little or no relevance to allergic symptoms. Most IgE‐binding glycans recognized up to 2008 were considered to be “classical” cross‐reactive carbohydrate determinants (CCD) that occur in insects, some helminths and throughout the plant kingdom. Since 2008, the prevailing opinion on lack of clinical relevance of IgE‐binding glycans has been subject to a reevaluation. This was because IgE specific for the mammalian disaccharide galactose‐alpha‐1,3‐galactose (alpha‐gal) was identified as a cause of delayed anaphylaxis to mammalian meat in the United States, an observation that has been confirmed by allergists in many parts of the world. Several experimental studies have shown that oligosaccharides with one or more terminal alpha‐gal epitopes can be attached as a hapten to many different mammalian proteins or lipids. The classical CCDs also behave like haptens since they can be expressed on proteins from multiple species. This is the explanation for extensive in vitro cross‐reactivity related to CCDs. Because of these developments, the Allergen Nomenclature Sub‐Committee recently decided to include glycans as potentially allergenic epitopes in an adjunct section of its website (www.allergen.org). In this article, the features of the main glycan groups known to be involved in IgE recognition are revisited, and their characteristic structural, functional, and clinical features are discussed.
Bridging Materiality and Subjectivity: Expanding the Commons in Cooperation Birmingham
Authors: Ruiz Cayuela Sergio 
Published: March 2021

AbstractExpansion is a matter of survival for emancipatory commons, permanently threatened by enclosure and cooptation. In this paper, I draw from my experience within Cooperation Birmingham to propose a theory (and practice) for expanding the commons that bridges two seemingly conflicting approaches. On the one hand, the concepts of “boundary commoning” and “commons ecologies” proposed by Massimo De Angelis, concerned with social reproduction and material autonomy. And on the other, “expanding commoning” as developed by Stavros Stavrides, which focuses on radical openness and the production of commoning subjectivities. I demonstrate how in organising a mutual aid response to the Covid‐19 pandemic, Cooperation Birmingham is using an expansion strategy that productively articulates both approaches. Boundary commoning and expanding commoning reinforce each other in the construction of a commons ecology that aims at posing a material alternative to capitalist social organisation while remaining always in‐the‐making and open to new commoners.
Early closure mechanisms of the ductus arteriosus in immature infants
Authors: Hallman Mikko , Treluyer Jean Marc , Aikio Outi , Rozé Jean‐Christophe 
Published: March 2021

AbstractAimAccording to experimental studies, cardiopulmonary distress decreases after closure of patent ductus arteriosus. However, early closure of the ductus using ibuprofen or indomethacin has failed to increase survival without serious morbidity. We review relevant data aiming to define optimal early management strategies that promote early closure of ductus arteriosus without serious adverse effects.MethodsLiterature in English was searched selectively focusing on the potential of using acetaminophen for early closure of the ductus.ResultsProphylactic ibuprofen or indomethacin intended to close the ductus, predisposes infants to ischaemia, bleeding and immune dysfunction. Acetaminophen appears to have a similar efficacy as indomethacin or ibuprofen, and all three dose‐dependently constrict the ductus. Ibuprofen and indomethacin cause non‐specific inhibition of prostaglandin synthesis, while acetaminophen predominantly inhibits prostaglandin E synthesis. Owing to low CYP450 activity in infancy, acetaminophen toxicity has been rarely evident. However, increasing the dosage increases the oxidative stress. We review prophylactic treatments that may increase the safety and efficacy of acetaminophen. These include vitamin A, cysteine and glutamine, and low‐dose corticosteroid supplementation.ConclusionThe current challenge is to define a safe perinatal management practice that promotes cardiorespiratory adaptation in immature infants, particularly the seamless closure of the ductus before significant cardiopulmonary distress develops.
Allergic contact dermatitis from potassium sorbate and sorbic acid in topical pharmaceuticals and medical devices
Authors: Dendooven Ella , Kerre Stefan , Foubert Kenn , Pieters Luc , Lambert Julien , Goossens An , Aerts Olivier 
Published: March 2021

AbstractBackgroundThe preservatives sorbic acid (SA) and potassium sorbate (PS) are considered rare skin sensitizers. PS‐containing products always contain SA to a certain extent, and positivity to PS may reflect sensitization to SA. Their optimal patch test conditions are unknown.ObjectivesTo report on the outcome of testing with SA and PS in various concentrations and/or vehicles.Patients and methodsSeventeen patients with allergic contact dermatitis from PS/SA‐containing topical pharmaceuticals and medical devices were patch tested to SA 2% and 5% pet.; SA 1%, 2%, 3%, 5%. eth.; and/or SA 2% aq., whereas PS was patch tested 5% pet. and/or 5% aq.ResultsOnly one patient, not tested to the ethanol preparations, presented with a (doubtful) positive reaction to SA 2% pet., while this remained negative in 13 patients who reacted to SA 2% eth. The preparations containing SA 5% pet.; 1%, 3%, and 5% eth.; and SA 2% aq. had little or no additional value. PS 5% pet. performed better than 5% aq., and always mirrored SA sensitization.ConclusionsSensitization to SA and PS is probably underestimated. SA 2% eth. and PS 5% pet. are preferred for patch testing, and patients sensitized to SA should avoid PS‐containing products.
Lessons from old fenced plots: Eco‐cultural Impacts of feral ungulates and potential decline in sea‐level rise resilience of coastal floodplains in northern Australia
Authors: Sloane Daniel R. , Ens Emilie , Wunungmurra Yumutjin , Gumana Yinimala , Wunungmurra Bandibandi , Wirrpanda Manman , Towler Gillian , Preece David , Rangers Yirralka 
Published: March 2021

SummaryManagement of feral animals can be complicated by conflicting economic, social, cultural and political values of stakeholders. To visually demonstrate the ecological impacts of feral ungulates, natural resource managers often construct exclusion fences; however, lessons are not often widely shared in the scientific literature and Indigenous insights are rarely recorded. Here, we report on long‐term (7–11 years) feral buffalo and pig exclusion fences that were constructed by the Yirralka Rangers in ephemeral coastal wetlands of the Laynhapuy Indigenous Protected Area, northern Australia. Elevation transects across fence boundaries suggested that feral ungulates may be eroding floodplains and therefore reducing elevation. Comparisons of intermittent photos and contemporary inside–outside fence floristic assessments suggested that feral ungulates have an obvious and significant effect on vegetation cover and composition which may also inhibit natural soil accretion. Interviews with senior Indigenous knowledge holders revealed that feral ungulate culling was broadly supported due to impacts on cultural and spiritual values. Synthesis of the results suggested that feral ungulates are having substantial impacts on the cultural use, flora and soil stabilisation of coastal wetlands. Further research on soil erosion and accretion in places with and without ungulates will elucidate the effects of ungulates on potential sea‐level rise resilience of coastal wetlands. This paper highlights the benefits of cross‐cultural and collaborative multi‐disciplinary research such as producing holistic outcomes relevant to stakeholders that can inform management decisions.