bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estimating the cost of antibiotic use on future collateral resistance: a retrospective comparison of cefuroxime versus cefazolin and amoxicillin/clavulanate
Authors: Chowers Michal , Zehavi Tamir , Gottesman Bat-Sheva , Baraz Avi , Nevo Daniel , Obolski Uri 
Published: January 2022

AbstractBackgroundQuantitative estimates of collateral resistance induced by antibiotic use are scarce. This study compared the effects of treatment with amoxicillin/clavulanate or cefazolin, compared to cefuroxime, on future resistance to ceftazidime among hospitalized patients.MethodsA retrospective analysis of patients with positive bacterial cultures hospitalized in an Israeli hospital during 2016-2019 was conducted. Patients were restricted to those treated with either amoxicillin/clavulanate, cefazolin, or cefuroxime and re-hospitalized with a positive bacterial culture during the following year. A 1:1 matching was performed for each patient in the amoxicillin/clavulanate and cefazolin groups, to a single patient from the cefuroxime group, yielding 185:185 and 298:298 matched patients. Logistic regression and g-formula (standardization) were used to estimate the odds ratio (OR), risk difference (RD), and number needed to harm (NNH).ResultsCefuroxime induced significantly higher resistance to ceftazidime than amoxicillin/clavulanate or cefazolin: the marginal OR was 1.76)95%CI 1.16-2.83) compared to amoxicillin/clavulanate, and 1.98 (95%CI 1.41-2.8) compared to cefazolin; The RD was 0.118 (95%CI 0.031-0.215) compared to amoxicillin/clavulanate, and 0.131 (95%CI 0.058-0.197) compared to cefazolin. We also estimated the NNH: replacing amoxicillin/clavulanate or cefazolin with cefuroxime would yield ceftazidime-resistance in one more patient for every 8.5 (95% CI 4.66-32.14) or 7.6 (95% CI 5.1-17.3) patients re-hospitalized in the following year.ConclusionsOur results indicate that treatment with amoxicillin/clavulanate or cefazolin is preferable to cefuroxime, in terms of future collateral resistance. The results presented here are a first step towards quantitative estimations of the ecological damage caused by different antibiotics.Key pointsWe performed a retrospective study estimating collateral resistance of treatment with cefuroxime relative to amoxicillin/clavulanate or cefazolin. Application of novel analytical methods allowed us to estimate the number needed to harm and hence ecological damage of the different treatments.
Infectious viral load in unvaccinated and vaccinated patients infected with SARS-CoV-2 WT, Delta and Omicron
Authors: Puhach Olha , Adea Kenneth , Hulo Nicolas , Sattonnet Pascale , Genecand Camille , Iten Anne , Bausch Frédérique Jacquérioz , Kaiser Laurent , Vetter Pauline , Eckerle Isabella , Meyer Benjamin 
Published: January 2022

AbstractBackgroundViral load (VL) is one determinant of secondary transmission of SARS-CoV-2. Emergence of variants of concerns (VOC) Alpha and Delta was ascribed, at least partly, to higher VL. Furthermore, with parts of the population vaccinated, knowledge on VL in vaccine-breakthrough infections is crucial. As RNA VL is only a weak proxy for infectiousness, studies on infectious virus presence by cell culture isolation are of importance.MethodsWe assessed nasopharyngeal swabs of COVID-19 patients for quantitative infectious viral titres (IVT) by focus-forming assay and compared to overall virus isolation success and RNA genome copies. We assessed IVTs during the first 5 symptomatic days in a total of 384 patients: unvaccinated individuals infected with pre-VOC SARS-CoV-2 (n= 118) or Delta (n= 127) and vaccine breakthrough infections with Delta (n= 121) or Omicron (n=18).FindingsCorrelation between RNA copy number and IVT was low for all groups. No correlation between IVTs and age or sex was seen. We observed higher RNA genome copies in pre-VOC SARS-CoV-2 compared to Delta, but significantly higher IVTs in Delta infected individuals. Vaccinated Delta infected individuals had significantly lower RNA genome copies and IVTs compared to unvaccinated subjects and cleared virus faster. In addition, vaccinated individuals with Omicron infection had comparable IVTs to Delta breakthrough infections.InterpretationQuantitative IVTs can give detailed insights into virus shedding kinetics. Vaccination was associated with lower infectious titres and faster clearance for Delta, showing that vaccination would also lower transmission risk. Omicron vaccine-breakthrough infections did not show elevated IVTs compared to Delta, suggesting that other mechanisms than increase VL contribute to the high infectiousness of Omicron.FundingThis work was supported by the Swiss National Science Foundation 196644, 196383, NRP (National Research Program) 78 Covid-19 Grant 198412, the Fondation Ancrage Bienfaisance du Groupe Pictet and the Fondation Privée des Hôpitaux Universitaires de Genève.
Molnupiravir combined with different repurposed drugs further inhibits SARS-CoV-2 infection in human nasal epithelium in vitro
Authors: Jonsdottir Hulda R. , Siegrist Denise , Julien Thomas , Padey Blandine , Bouveret Mendy , Terrier Olivier , Pizzorno Andres , Huang Song , Samby Kirandeep , Wells Timothy N.C. , Boda Bernadett , Rosa-Calatrava Manuel , Engler Olivier B. , Constant Samuel 
Published: January 2022

AbstractThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first identified in late 2019, has caused a worldwide pandemic with unprecedented economic and societal impact. Currently, several vaccines are available, and multitudes of antiviral treatments have been proposed and tested. Although many of the vaccines show high clinical efficacy, they are not equally accessible worldwide. Additionally, due to the continuous emergence of new virus variants, and generally short duration of immunity, the development of safe and effective antiviral treatments remains of the utmost importance. Since the emergence of SARS-CoV-2, substantial efforts have been undertaken to repurpose existing and approved drugs for accelerated clinical testing and potential emergency use authorizations. However, drug-repurposing using high throughput screenings in cellular assays, often identify hits that later prove ineffective in clinical studies. Our approach was to evaluate the activity of compounds that have either been tested clinically or already undergone extensive preclinical profiling, using a standardized in vitro model of human nasal epithelium. Secondly, we evaluated drug combinations using sub-maximal doses of each active single compound. Here, we report the antiviral effects of 95 single compounds and 30 combinations. The data show that selected drug combinations including 10 μM of molnupiravir, a viral RNA-dependent RNA polymerase (RdRp) inhibitor, effectively inhibit SARS-CoV-2 replication. This indicates that such combinations are worthy of further evaluation as potential treatment strategies against coronavirus disease 2019 (COVID-19).
Exploring high-resolution cryo-ET and subtomogram averaging capabilities of contemporary DEDs
Authors: Obr Martin , Hagen Wim JH , Dick Robert A , Yu Lingbo , Kotecha Abhay , Schur Florian KM 
Published: January 2022

AbstractThe potential of energy filtering and direct electron detection for cryo-electron microscopy (cryo-EM) image processing has been well documented for single particle analysis (SPA). Here, we assess the performance of recently introduced hardware for cryo-electron tomography (cryo-ET) and subtomogram averaging (STA), an increasingly popular structural determination method for complex 3D specimens. We acquired cryo-ET datasets of EIAV virus-like particles (VLPs) on two contemporary cryo-EM systems equipped with different energy filters and direct electron detectors (DED), specifically a Krios G4, equipped with a cold field emission gun (CFEG), Thermo Fisher Scientific Selectris X energy filter, and a Falcon 4 DED; and a Krios G3i, with a Schottky field emission gun (XFEG), a Gatan Bioquantum energy filter, and a K3 DED. We performed constrained cross-correlation-based STA on equally sized datasets acquired on the respective systems. The resulting EIAV CA hexamer reconstructions show that both systems perform comparably in the 4-6 Å resolution range. In addition, by employing a recently introduced multiparticle refinement approach, we obtained a reconstruction of the EIAV CA hexamer at 2.9 Å. Our results demonstrate the potential of the new generation of energy filters and DEDs for STA, and the effects of using different processing pipelines on their STA outcomes.
The genomic landscape of contemporary western Remote Oceanians
Authors: Arauna Lara R. , Bergstedt Jacob , Choin Jeremy , Mendoza-Revilla Javier , Harmant Christine , Roux Maguelonne , Mas-Sandoval Alex , Lémée Laure , Colleran Heidi , François Alexandre , Valentin Frédérique , Cassar Olivier , Gessain Antoine , Quintana-Murci Lluis , Patin Etienne 
Published: January 2022

SUMMARYThe Vanuatu archipelago served as a gateway to Remote Oceania during one of the most extensive human migrations to uninhabited lands, ~3,000 years ago. Ancient DNA studies suggest an initial settlement by East Asian-related peoples that was quickly followed by the arrival of Papuan-related populations, leading to a major population turnover. Yet, there is uncertainty over the population processes and the sociocultural factors that have shaped the genomic diversity of ni-Vanuatu, who present nowadays among the world’s highest linguistic and cultural diversity. Here, we report new genome-wide data for 1,433 contemporary ni-Vanuatu from 29 different islands, including 287 couples. We find that ni-Vanuatu derive their East Asian- and Papuan-related ancestry from the same source populations and descend from relatively synchronous, sex-biased admixture events that occurred ~1,700-2,300 years ago, indicating a peopling history common to all the archipelago. However, East Asian-related ancestry proportions differ markedly across islands, suggesting that the Papuan-related population turnover was geographically uneven. Furthermore, we detect Polynesian ancestry arriving ~600-1,000 years ago to South Vanuatu in both Polynesian- and non-Polynesian-speaking populations. Lastly, we provide evidence for a tendency of spouses to carry similar genetic ancestry, when accounting for relatedness avoidance. The signal is not driven by strong genetic effects of specific loci or trait-associated variants, suggesting that it results instead from social assortative mating. Altogether, our findings provide insight into both the genetic history of ni-Vanuatu populations and how sociocultural processes have shaped the diversity of their genomes.
Active site geometry stabilization of a presenilin homolog by the lipid bilayer promotes intramembrane proteolysis
Authors: Feilen Lukas P. , Chen Shu-Yu , Fukumori Akio , Feederle Regina , Zacharias Martin , Steiner Harald 
Published: January 2022

ABSTRACTCleavage of membrane proteins in the lipid bilayer by intramembrane proteases is crucial for health and disease. Although different lipid environments can potently modulate their activity, how this is linked to their structural dynamics is unclear. Here we show that the carboxy-peptidase-like activity of the archaeal intramembrane protease PSH, a homolog of the Alzheimeŕs disease-associated presenilin/γ-secretase is impaired in micelles and promoted in a lipid bilayer. Comparative molecular dynamics simulations revealed that important elements for substrate binding such as transmembrane domain 6a of PSH are more labile in micelles and stabilized in the lipid bilayer. Moreover, consistent with an enhanced interaction of PSH with a transition- state analog inhibitor, the bilayer promoted the formation of the enzymés catalytic active site geometry. Our data indicate that the lipid environment of an intramembrane protease plays a critical role in structural stabilization and active site arrangement of the enzyme-substrate complex thereby promoting intramembrane proteolysis.
Multi-cancer classification; an analysis of neural network complexity
Authors: Webber James W. , Elias Kevin 
Published: January 2022

AbstractBackgroundCancer identification is generally framed as binary classification, normally discrimination of a control group from a single cancer group. However, such models lack any cancer-specific information, as they are only trained on one cancer type. The models fail to account for competing cancer risks. For example, an ostensibly healthy individual may have any number of different cancer types, and a tumor may originate from one of several primary sites. Pan-cancer evaluation requires a model trained on multiple cancer types, and controls, simultaneously, so that a physician can be directed to the correct area of the body for further testing.MethodsWe introduce novel neural network models to address multi-cancer classification problems across several data types commonly applied in cancer prediction, including circulating miRNA expression, protein, and mRNA. In particular, we present an analysis of neural network depth and complexity, and investigate how this relates to classification performance. Comparisons of our models with state-of-the-art neural networks from the literature are also presented.ResultsOur analysis evidences that shallow, feed-forward neural net architectures offer greater performance when compared to more complex deep feed-forward, Convolutional Neural Network (CNN), and Graph CNN (GCNN) architectures considered in the literature.ConclusionThe results show that multiple cancers and controls can be classified accurately using the proposed models, across a range of expression technologies in cancer prediction.ImpactThis study addresses the important problem of pan-cancer classification, which is often overlooked in the literature. The promising results highlight the urgency for further research.
The Psychosocial Benefits of Sport Participation During COVID-19 Are Only Partially Explained by Increased Physical Activity
Authors: Watson Andrew M. , Biese Kevin , Reardon Claudia , Schwarz Allison , Haraldsdottir Kristin , Brooks M. Alison , Bell David R. , McGuine Timothy 
Published: January 2022

ABSTRACTThe purpose of this study was to determine whether physical activity (PA) increases were responsible for the improvements in mental health and quality of life (QOL) seen among adolescents who returned to sport during the COVID-19 pandemic.Adolescent athletes were asked to complete a survey in October 2020 regarding demographic information, whether they had returned to sport participation (no [DNP], yes [PLY]), school instruction type (virtual, in-person, hybrid), anxiety, depression, QOL, and PA. Anxiety, depression, QOL and PA were compared between PLY and DNP using least squares means from linear models adjusted for age, gender, and instruction type. Mediation analysis assessed whether the relationship between sport status and anxiety, depression, and QOL was mediated by PA. 171 athletes had returned to play, while 388 had not. PLY athletes had significantly lower anxiety (3.6±0.4 v 8.2±0.6, p<0.001) and depression (4.2±0.4 v 7.3±0.6, p<0.001), and significantly higher QOL (88.1±1.0 v 80.2±1.4, p<0.001) and PA (24.0±0.5 v 16.3±0.7, p<0.001). PA explained a significant, but relatively small portion of the difference in depression (22.1%, p=0.02) and QOL (16.0%, p=0.048) between PLY and DNP athletes, but did not explain the difference in anxiety (6.6%, p=0.20). Increased PA is only responsible for a small portion of the improvements in depression and QOL among athletes who returned to sports and unrelated to improvements in anxiety. This suggests that the majority of the mental health benefits of sport participation for adolescents during the COVID-19 pandemic are independent of, and in addition to, the benefits of increased PA.
Exploring the nexus of social media influencers and consumer brand engagement
Authors: Cheung Man Lai , Leung Wilson K.S. , Yang Morgan X. , Koay Kian Yeik , Chang Man Kit 
Published: January 2022

PurposeGrounded in uses and gratification theory (UGT) and observational learning theory (OLT), this study aims to understand the impact of motivational factors on consumer-influencer engagement behaviors (CIEBs). Motivating factors, including entertainment, information seeking, reward and social interaction, are regarded as antecedents of consumers' OLT, as manifested by CIEB dimensions, including consumption, contribution and creation, and subsequently drive consumer engagement with the endorsed brands.Design/methodology/approachA self-administered questionnaire was distributed to Malaysian social media users. A total of 263 responses were collected and analyzed using partial least squares structural equation modeling (PLS-SEM) to examine the impact of motivational factors on CIEBs.FindingsThe results show that the three dimensions of CIEBs can be predicted by different gratifications (information seeking, entertainment, reward and interaction). In addition, two of the CIEB dimensions, consumption and contribution, were found to have a significant positive influence on consumers' engagement with endorsed brands.Practical implicationsThis study provides insights into how social media influencers (SMIs) could lead to CIEBs by creating entertaining and rewarding content that facilitates social interaction between consumers. SMIs and marketers that encourage consumers to browse, comment and share SMI-created posts will enhance consumer engagement with the endorsed brands, as engagement is driven by the consumption and contribution to SMI-created content.Originality/valueSMI marketing is increasing, and many brands are beginning to rely more on SMIs to promote brands. Yet, there is a dearth of studies that have examined how SMIs play a role in affecting consumers' engagement with endorsed brands. This study contributes to the marketing literature by developing and empirically testing the research model. Results suggest that social interaction, reward and entertainment are key motivational factors that drive CIEBs, which, in turn, foster consumer engagement with endorsed brands.
Sustainable development early warning and financing risk management of resource-based industrial clusters using optimization algorithms
Authors: Wang Yawen , Xue Weixian 
Published: January 2022

PurposeThe purpose is to analyze and discuss the sustainable development (SD) and financing risk assessment (FRA) of resource-based industrial clusters under the Internet of Things (IoT) economy and promote the application of Machine Learning methods and intelligent optimization algorithms in FRA.Design/methodology/approachThis study used the Support Vector Machine (SVM) algorithm that is analyzed together with the Genetic Algorithm (GA) and Ant Colony Optimization (ACO) algorithm. First, Yulin City in Shaanxi Province is selected for case analysis. Then, resource-based industrial clusters are studied, and an SD early-warning model is implemented. Then, the financing Risk Assessment Index System is established from the perspective of construction-operation-transfer. Finally, the risk assessment results of Support Vector Regression (SVR) and ACO-based SVR (ACO-SVR) are analyzed.FindingsThe results show that the overall sustainability of resource-based industrial clusters and IoT industrial clusters is good in the Yulin City of Shaanxi Province, and the early warning model of GA-based SVR (GA-SVR) has been achieved good results. Yulin City shows an excellent SD momentum in the resource-based industrial cluster, but there are still some risks. Therefore, it is necessary to promote the industrial structure of SD and improve the stability of the resource-based industrial cluster for Yulin City.Originality/valueThe results can provide a direction for the research on the early warning and evaluation of the SD-oriented resource-based industrial clusters and the IoT industrial clusters, promoting the application of SVM technology in the engineering field.
Research trends in tourism and hospitality from 1991 to 2020: an integrated approach of corpus linguistics and bibliometrics
Authors: Wang Gui , Wang Hui , Wang Li 
Published: January 2022

PurposeThis study aims to track the historical development in tourism and hospitality research over the past 30 years by applying a novel interdisciplinary approach, combining both corpus linguistics and bibliometric analysis.Design/methodology/approachMost frequently discussed topics and newly emerging topics were identified by investigating 18,266 abstracts from 18 leading tourism and hospitality journals with corpus linguistics toolkit AntConc and natural language processing (NLP) tool spaCy. Trend analysis and bibliometric methods were used to determine the longitudinal changes of research topics, most highly-cited publications and authors' production.FindingsThis study revealed the evolution patterns of the identified 576 most frequently discussed topics across the four subperiods (1991–2000, 2001–2010, 2011–2015 and 2016–2020). Specifically, results showed that information technology-related topics account for the largest proportion of the identified 38 newly emerging topics from 2011. Besides, researchers are increasingly focusing on the use of more sophisticated and advanced statistical methodologies.Practical implicationsThis study helps researchers make sensible decisions on what research topics to explore; it also helps practitioners and stakeholders make the shift and track opportunities in the field.Originality/valueNo other studies have employed the novel interdisciplinary approach, combining corpus linguistic tools in linguistics, NLP techniques in computer science and bibliometric analysis in library and information science, for exploring research trends in tourism and hospitality.
Urbanization and the organization of territorial cohesion – results from a comparative Danish case-study on territorial inequality and social cohesion
Authors: Jørgensen Anja , Fallov Mia Arp 
Published: January 2022

PurposeThere is a growing importance for public facilitation of corporate social responsibility and involvement of civil organizations in securing territorial cohesion and development. In the present article, the authors focus on how we are to understand a locally sensitive organization of territorial cohesion in the Danish context. Traditional sociological concepts and standardized area-types used for administrative purposes have turned out not being very helpful in understanding the interrelation between inequality, urbanization and territorial cohesion. The authors argue for a processual and relational approach to urbanization.Design/methodology/approachThe present article is based on interview material and policy documents from three Danish case studies representing urban, suburban and rural forms of settlement. The case studies are part of a cross-European research project.FindingsThe authors show how territorial governance play a key role in the strategies of densification/de-densification facilitating shielding capacities of collective efficacy, and reversely that bottom-up innovations are crucial for the ability of territorial governance to mobilize territorial capital and mediate in effects of territorial inequality. Spatial imaginaries legitimize these efforts to organize cohesion. The spatial imaginaries work as common frame of references for the interplay between strategies of (de)densification and collective efficacy, and they activate particular balances between growth agendas and everyday life.Originality/valueThese findings represent an original perspective on how and why urbanization impact on places in a more specific and variated way than often portrayed as it highlight how social capacities tied to place might work with or against existing social, economic and cultural structures shaping territorial cohesion.