bluuebunny/crossref_metadata_2025_split huggingface dataset:
The production of Necator americanus larvae for use in experimental human infection
Authors: Chapman Paul R. , Llewellyn Stacey , Jennings Helen , Becker Luke , Giacomin Paul , McDougall Rodney , Robson Jennifer , Loukas Alex , McCarthy James 
Published: July 2022

Abstract
Background
Although there is unprecedented interest in experimental human hookworm infection, details of hookworm manufacture and characterisation have been sparsely reported. In this report, we detail the production and characterisation of Necator americanus larvae for use in a recently published clinical trial.

Methods
Faeces was obtained from an experimentally infected donor. Faecal hookworm DNA was determined by quantitative PCR. Paired samples were incubated in either sterile water or sterile water mixed with antimicrobials (amphotericin and gentamicin). Coproculture was performed by modified Harada-Mori method. The harvested larvae were then processed in either sterile water or antiseptic solution. Larval yield was then calculated (larvae per gram), larval viability was determined by thermally induced motility assay and microbial burden was determined at the day of harvest, at 48 h and at 7 days.

Results
Twenty-eight faecal cultures were performed over 16 months. The faecal hookworm DNA content was variable over this time. There was no association of larval yield with faecal hookworm DNA content. Pre-treatment of faeces with antimicrobials did not influence larval yield. Larval motility was 85.3% (95% CI 79.3–91.3%). Incubation of larvae in antiseptics did not reduce viability at 14 days with a marginal mean of 68.6% (95% CI 59.1–78.1%) washed in water vs. 63.3% (95% CI 53.8 – 72.9%) when incubated in betadine (p = 0.38). Larvae washed in sterile water did not meet microbial bioburden criteria. Incubation in antiseptic resulted in acceptable microbial bioburden at 48 h but not at 7 days. Although the addition of gentamicin did reduce the microbial bio-burden acceptable levels, it was found to significantly lower larval motility at 7 days compared to incubation in sterile water and motility at 7 days 37.8% (95% CI 4.7–70.9%) vs. 67.3% (95% CI 35.2–99.3%, p < 0.001), respectively.

Conclusions
Despite standardised culture methodologies and the use of a single donor, larval yield varied considerably between batches and had no association with faecal hookworm DNA. Larval viability decreases over time and the age of larvae at time of use are likely to be important. Microbial bioburden maybe temporarily reduced by incubation in antiseptics and has little effect on viability. Incubation of larvae in gentamicin is effective at reducing microbial bioburden but is deleterious to larval viability.

Graphical Abstract
In silico prediction of UGT-mediated metabolism in drug-like molecules via graph neural network
Authors: Huang Mengting , Lou Chaofeng , Wu Zengrui , Li Weihua , Lee Philip W. , Tang Yun , Liu Guixia 
Published: July 2022

AbstractUDP-glucuronosyltransferases (UGTs) have gained increasing attention as they play important roles in the phase II metabolism of drugs. Due to the time-consuming process and high cost of experimental approaches to identify the metabolic fate of UGT enzymes, in silico methods have been developed to predict the UGT-mediated metabolism of drug-like molecules. We developed consensus models with the combination of machine learning (ML) and graph neural network (GNN) methods to predict if a drug-like molecule is a potential UGT substrate, and then we applied the Weisfeiler-Lehman Network (WLN) model to identify the sites of metabolism (SOMs) of UGT-catalyzed substrates. For the substrate model, the accuracy of the single substrate prediction model on the test set could reach to 0.835. Compared with the single estimators, the consensus models are more stable and have better generalization ability, and the accuracy on the test set reached to 0.851. For the SOM model, the top-1 accuracy of the SOM model on the test set reached to 0.898, outperforming existing works. Thus, in this study, we proposed a computational framework, named Meta-UGT, which would provide a useful tool for the prediction and optimization of metabolic profiles and drug design.
Graphical Abstract
Evaluation of immunogenicity and cross-reactive responses of vaccines prepared from two chimeric serotype O foot-and-mouth disease viruses in pigs and cattle
Authors: Li Pinghua , Huang Shulun , Zha Jingjing , Sun Pun , Li Dong , Bao Huifang , Cao Yimei , Bai Xingwen , Fu Yuanfang , Ma Xueqing , Li Kun , Yuan Hong , Zhang Jing , Zhao Zhixun , Wang Jian , Zhang Keqiang , Chen Yingli , Zhang Qiang , Qi Shuyun , Liu Zaixin , Lu Zengjun 
Published: July 2022

AbstractFoot-and-mouth disease (FMD) remains a very serious barrier to agricultural development and the international trade of animals and animal products. Recently, serotype O has been the most prevalent FMDV serotype in China, and it has evolved into four different lineages: O/SEA/Mya-98, O/ME-SA/PanAsia, O/ME-SA/Ind-2001 and O/Cathay. PanAsia-2, belonging to the O/ME-SA topotype, is prevalent in neighbouring countries and poses the risk of cross-border spread in China. This study aimed to develop a promising vaccine candidate strain that can not only provide the best protection against all serotype O FMDVs circulating in China but also be used as an emergency vaccine for the prevention and control of transboundary incursion of PanAsia-2. Here, two chimeric FMDVs (rHN/TURVP1 and rHN/NXVP1) featuring substitution of VP1 genes of the O/TUR/5/2009 vaccine strain (PanAsia-2) and O/NXYCh/CHA/2018 epidemic strain (Mya98) were constructed and evaluated. The biological properties of the two chimeric FMDVs were similar to those of the wild-type (wt) virus despite slight differences in plaque sizes observed in BHK-21 cells. The structural protein-specific antibody titres induced by the rHN/TURVP1 and wt virus vaccines in pigs and cows were higher than those induced by the rHN/NXVP1 vaccine at 28–56 dpv. The vaccines prepared from the two chimeric viruses and wt virus all induced the production of protective cross-neutralizing antibodies against the viruses of the Mya-98, PanAsia and Ind-2001 lineages in pigs and cattle at 28 dpv; however, only the animals vaccinated with the rHN/TURVP1 vaccine produced a protective immune response to the field isolate of the Cathay lineage at 28 dpv, whereas the animals receiving the wt virus and the rHN/NXVP1 vaccines did not, although the wt virus and O/GXCX/CHA/2018 both belong to the Cathay topotype. This study will provide very useful information to help develop a potential vaccine candidate for the prevention and control of serotype O FMD in China.
Comparative pathogenesis of peste des petits ruminants virus strains of difference virulence
Authors: Eloiflin Roger-Junior , Grau-Roma Llorenç , Python Sylvie , Mehinagic Kemal , Godel Aurélie , Libeau Geneviève , Summerfield Artur , Bataille Arnaud , García-Nicolás Obdulio 
Published: July 2022

AbstractPeste des petits ruminants (PPR) is an acute disease of small ruminants caused by a morbillivirus. Clinical observation of the disease in the field revealed that several species of small ruminants are affected to varying degrees. This difference in disease-related effects could depend either on the host or on the virulence of the virus strain. A previous study highlighted the difference in virulence between two strains of PPRV used to infect Saanen goats. For this breed, PPRV Morocco 2008 strain (MA08) was highly virulent while PPRV Côte d’Ivoire 1989 (IC89) strain induced mild disease. Experimental studies generally based on healthy and young animals do not permit exploration of the natural variability of the host susceptibility to PPRV. Therefore, building on the previous study on Saanen goats, the current study focussed on this breed of goat and used commercially available animals with an unknown history of infection with other pathogens. Results confirmed the previous disease pattern for PPRV IC89 and MA08 strains. Viral RNA detection, macroscopic and histological lesions were stronger for the highly virulent MA08 strain. We show here for the first time that viral RNA can be detected in the tissues of vaccinated animals. Viral RNA was also detected for the first time in serum samples, which is in agreement with the role of circulating immune cells in transporting the virus into host target organs. Thus, this study provides insight into the pathogenesis of strains of different virulence of PPRV and will help to better understand the onset of the disease.
Antimicrobial resistance control in the emergency department: a need for concrete improvement
Authors: Pin Martin , Somasundaram Rajan , Wrede Christian , Schwab Frank , Gastmeier Petra , Hansen Sonja 
Published: July 2022

Abstract
Background
Rational use of antibiotics (AB) and infection prevention and control (IPC) are key measures for reducing antimicrobial resistance (AMR) in healthcare. Nonetheless, transferring evidence into clinical practice in emergency medicine has proven difficult. The extent to which structural requirements for implementing AMR control exist in German emergency departments (ED) was determined in a survey.

Methods
Aspects of antimicrobial stewardship (AMS) and IPC implementation were surveyed within the German Association for Emergency Medicine (Deutsche Gesellschaft interdisziplinäre Notfall- und Akutmedizin e.V, DGINA) in 2018. Data were collected using an anonymous online questionnaire on ED characteristics, ED-based-link personnel for IPC and AMS, education and training, process monitoring and specific requirements for AMS and IPC as availability of AMR data and alcohol-based hand rub (AHR) consumption data. Data were analysed descriptively.

Results
66 EDs with in median [interquartile range (IQR)] of 30,900 [23,000; 40,000] patient visits participated in the survey. EDs’ healthcare worker (HCW) received regular training on hand hygiene (HH) in 67% and on AMS in 20% of EDs. Surveillance of AHR consumption was performed by 73% EDs, surveillance of AB consumption by 64%. Regular audits on HH were performed in 39%. Training and audit activities, showed no significant variations according to EDs’ organizational characteristics. HCWs received immediate feedback of HH performance in 29%, in 23% a regular structured feedback of HH was provided. ED-based physicians with (1) specific IPC responsibilities and training were available in 61%, with (2) AMS training and responsibility in 15%. 83% had ED based IPC link nurses with precise IPC responsibilities in place. Essentially resistance data existed at the hospital level (74%) rather than at ED- or regional level (15% and 14% respectively).

Conclusions
Management of AMR varies in German EDs, especially in accordance to hospital size and level of emergency care. IPC seems to receive more attention than AMS. Our data indicate the need for more implementation of regular IPC and AMS training in connection with monitoring and feedback in German EDs.
Glyphosate exposure deteriorates oocyte meiotic maturation via induction of organelle dysfunctions in pigs
Authors: Xing Chunhua , Chen Shun , Wang Yue , Pan Zhennan , Zou Yuanjing , Sun Shaochen , Ren Zili , Zhang Yu 
Published: July 2022

Abstract
Background
Recently, defects in mammalian oocytes maturation induced by environmental pollution results in the decreasing animal reproduction. Animal exposed to glyphosate is largely unavoidable because glyphosate is one of the most widely used herbicide worldwide due to its high-efficiency and broad-spectrum effects, which causes glyphosate an environmental contaminant found in soil, water and food. During the last few years, the growing and wider use of glyphosate has raised great concerns about its effects of reproductive toxicity. In this study, using porcine models, we investigated effects of glyphosate on organelle functions during oocyte meiosis.

Results
The results showed glyphosate exposure disrupted porcine oocyte maturation. Expression levels of cumulus expansion-related genes were interfered, further indicating the meiotic defects. The damaging effects were mediated by destruction of mitochondrial distribution and functions, which induced ROS accumulation and oxidative stress, also indicated by the decreased mRNA expression of related antioxidant enzyme genes. We also found an interference of endoplasmic reticulum (ER) distribution, disturbance of Ca2+ homeostasis, as well as fluctuation of ER stress, showing with the reduced ER stress-related mRNA or protein expression, which could indicate the dysfunction of ER for protein processing and signal transduction in glyphosate-exposed oocytes. Moreover, glyphosate exposure induced the disruption of lysosome function for autophagy, showing with the decrease of LAMP2 expression and autophagy-related genes mRNA expression. Additionally, our data showed the distribution of Golgi apparatus and the functions of ribosome were disturbed after glyphosate exposure, which might affect protein synthesis and transport.

Conclusions
Collectively, our study showed that exposed to glyphosate could affect animal reproduction by compromising the quality of oocytes through its wide toxic effects on organelle functions.
Phylogenies of the 16S rRNA gene and its hypervariable regions lack concordance with core genome phylogenies
Authors: Hassler Hayley B. , Probert Brett , Moore Carson , Lawson Elizabeth , Jackson Richard W. , Russell Brook T. , Richards Vincent P. 
Published: July 2022

AbstractBackgroundThe 16S rRNA gene is used extensively in bacterial phylogenetics, in species delineation, and now widely in microbiome studies. However, the gene suffers from intragenomic heterogeneity, and reports of recombination and an unreliable phylogenetic signal are accumulating. Here, we compare core gene phylogenies to phylogenies constructed using core gene concatenations to estimate the strength of signal for the 16S rRNA gene, its hypervariable regions, and all core genes at the intra- and inter-genus levels. Specifically, we perform four intra-genus analyses (Clostridium,n = 65;Legionella,n = 47;Staphylococcus,n = 36; andCampylobacter,n = 17) and one inter-genus analysis [41 core genera of the human gut microbiome (31 families, 17 orders, and 12 classes),n = 82].ResultsAt both taxonomic levels, the 16S rRNA gene was recombinant and subject to horizontal gene transfer. At the intra-genus level, the gene showed one of the lowest levels of concordance with the core genome phylogeny (50.7% average). Concordance for hypervariable regions was lower still, with entropy masking providing little to no benefit. A major factor influencing concordance was SNP count, which showed a positive logarithmic association. Using this relationship, we determined that 690 ± 110 SNPs were required for 80% concordance (average 16S rRNA gene SNP count was 254). We also found a wide range in 16S-23S-5S rRNA operon copy number among genomes (1–27). At the inter-genus level, concordance for the whole 16S rRNA gene was markedly higher (73.8% — 10th out of 49 loci); however, the most concordant hypervariable regions (V4, V3-V4, and V1-V2) ranked in the third quartile (62.5 to 60.0%).ConclusionsRamifications of a poor phylogenetic performance for the 16S rRNA gene are far reaching. For example, in addition to incorrect species/strain delineation and phylogenetic inference, it has the potential to confound community diversity metrics if phylogenetic information is incorporated — for example, with popular approaches such as Faith’s phylogenetic diversity and UniFrac. Our results highlight the problematic nature of these approaches and their use (along with entropy masking) is discouraged. Lastly, the wide range in 16S rRNA gene copy number among genomes also has a strong potential to confound diversity metrics.
Study protocol: a comprehensive multi-method neuroimaging approach to disentangle developmental effects and individual differences in second language learning
Authors: Menks W. M. , Ekerdt C. , Janzen G. , Kidd E. , Lemhöfer K. , Fernández G. , McQueen J. M. 
Published: July 2022

AbstractBackgroundWhile it is well established that second language (L2) learning success changes with age and across individuals, the underlying neural mechanisms responsible for this developmental shift and these individual differences are largely unknown. We will study the behavioral and neural factors that subserve new grammar and word learning in a large cross-sectional developmental sample. This study falls under theNWO(Nederlandse Organisatie voor Wetenschappelijk Onderzoek [Dutch Research Council]) Language in Interaction consortium (website:https://www.languageininteraction.nl/).MethodsWe will sample 360 healthy individuals across a broad age range between 8 and 25 years. In this paper, we describe the study design and protocol, which involves multiple study visits covering a comprehensive behavioral battery and extensive magnetic resonance imaging (MRI) protocols. On the basis of these measures, we will create behavioral and neural fingerprints that capture age-based and individual variability in new language learning. The behavioral fingerprint will be based on first and second language proficiency, memory systems, and executive functioning. We will map the neural fingerprint for each participant using the following MRI modalities: T1‐weighted, diffusion-weighted, resting-state functional MRI, and multiple functional-MRI paradigms. With respect to the functional MRI measures, half of the sample will learn grammatical features and half will learn words of a new language. Combining all individual fingerprints allows us to explore the neural maturation effects on grammar and word learning.DiscussionThis will be one of the largest neuroimaging studies to date that investigates the developmental shift in L2 learning covering preadolescence to adulthood. Our comprehensive approach of combining behavioral and neuroimaging data will contribute to the understanding of the mechanisms influencing this developmental shift and individual differences in new language learning. We aim to answer: (I) do these fingerprints differ according to age and can these explain the age-related differences observed in new language learning? And (II) which aspects of the behavioral and neural fingerprints explain individual differences (across and within ages) in grammar and word learning? The results of this study provide a unique opportunity to understand how the development of brain structure and function influence new language learning success.
Supporting Structured Data Capture for Patients With Cancer: An Initiative of the University of Wisconsin Carbone Cancer Center Survivorship Program to Improve Capture of Malignant Diagnosis and Cancer Staging Data
Authors: Emamekhoo Hamid , Carroll Cibele B. , Stietz Chelsea , Pier Jeffrey B. , Lavitschke Michael D. , Mulkerin Daniel , Sesto Mary E. , Tevaarwerk Amye J. 
Published: July 2022

PURPOSE Structured data elements within electronic health records are health-related information that can be entered, stored, and extracted in an organized manner at later time points. Tracking outcomes for cancer survivors is also enabled by structured data. We sought to increase structured data capture within oncology practices at multiple sites sharing the same electronic health records. METHODS Applying engineering approaches and the Plan-Do-Study-Act cycle, we launched dual quality improvement initiatives to ensure that a malignant diagnosis and stage were captured as structured data. Intervention: Close Visit Validation (CVV) requires providers to satisfy certain criteria before closing ambulatory encounters. CVV may be used to track open clinical encounters and chart delinquencies to encourage optimal clinical workflows. We added two cancer-specific required criteria at the time of closing encounters in oncology clinics: (1) the presence of at least one malignant diagnosis on the Problem List and (2) staging all the malignant diagnoses on the Problem List when appropriate. RESULTS Six months before the CVV implementation, the percentage of encounters with a malignant diagnosis on the Problem List at the time of the encounter was 65%, whereas the percentage of encounters with a staged diagnosis was 32%. Three months after cancer-specific CVV implementation, the percentages were 85% and 75%, respectively. Rates had increased to 90% and 88% more than 2 years after implementation. CONCLUSION Oncologist performance improved after the implementation of cancer-specific CVV criteria, with persistently high percentages of relevant malignant diagnoses and cancer stage structured data capture 2 years after the intervention.
Secret Laid Bare: Close Reading of Chinese Poetry
Authors: Lian Xinda 
Published: July 2022

Abstract
In the most exciting results of linguistic criticism of poetic function in classical Chinese poetry, one sees an ideal integration of microattention to texts and macroinvestigation of grammars of Chinese poetics. The greatest contribution of this close reading of the sinologist brand is the laying bare—in plain analytical language—of the mechanism of Chinese poetics, long grudgingly guarded as some ineffable (zhike yihui buke yanchuan 只可意會不可言傳) secret.
Feminist Theories and Women Writers of Late Imperial China: Impact and Critique
Authors: Fong Grace S. 
Published: July 2022

AbstractFeminism, feminist theory, feminist literary theory were already highly contentious in what they represented to Euro-American critics and theorists in the 1980s, when scholars in Chinese literary studies began sustained research on women writers in late imperial China (ca. 1600–1911). Their research drew on developments in Western feminist theories while problematizing certain applications. In this article, I review major debates in 1980s and 1990s Western feminist literary theory, divided by the different approaches of Anglo-American and French feminist critics and gender studies, examining why specific arguments on women and language, genres studied, and theoretical underpinnings did not hold significant relevance to the study of similar issues when applied to women's writing in pre-twentieth-century China. Yet certain concepts were highly fruitful in critical analysis. Feminist theory was never monolithic, even when it was Eurocentric; theories were drawn from a plurality of different disciplines and schools. Concepts that came into currency—gender, gaze, voice, agency, subjectivity, authorship, and so on—from poststructuralist, postcolonial, cultural, and film studies proved to be useful tools in feminist literary studies. Some came to be deployed in scholarship on women's literature in historical China. In this context, I reflect on theoretical approaches in significant studies of women's writing of late imperial China and consider the impact or critique this subfield of Chinese literary studies posed to Western feminist theories and broader questions of the applicability of modern/postmodern feminist theories to literature of earlier periods and other cultures before the globalization of the twentieth and twenty-first centuries.
Whither Theatricality? Toward Traditional Chinese Drama and Theater (Xiqu 戲曲) as World Theater
Authors: Sieber Patricia 
Published: July 2022

Abstract
The essay provides a brief review of how certain approaches to theatricality evolved in response to particular theatrical archives or repertoires in non-Chinese contexts. It then considers a number of recent studies of Chinese drama and theater in light of the following issues: the nature of theatrical language, the emergence and uses of fictionality, and the reconstruction of performance aesthetics. In focusing on these particular areas, the essay seeks to show how such research can contribute toward countering entrenched characterizations of xiqu as “non-drama,” “spectacle,” or “pure heritage.” The final section of the article proposes some future avenues of inquiry in order to deepen the dialogue between Sinology and theater studies while providing tools for sustaining the practice of xiqu and fostering broader appreciation of traditional Chinese theater in Anglophone, Chinese-speaking, and other contexts.