bluuebunny/crossref_metadata_2025 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

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

UDP-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

Foot-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

Peste 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

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

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

Background

The 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].

Results

At 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%).

Conclusions

Ramifications 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

Background

While 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/).

Methods

We 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.

Discussion

This 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.
Seismic reservoir characterization of the Gassum Formation in the Stenlille aquifer gas storage, Denmark — Part 1
Authors: Chopra Satinder , Sharma Ritesh Kumar , Bredesen Kenneth , Marfurt Kurt J.
Published: July 2022

Seismic reservoir characterization plays an important role in carbon capture and storage analysis. The Havnsø anticlinal structure in Denmark is a prospective CO2 storage site due to its proximity to two large emission sources—a coal-fired power station and a nearby refinery. Although legacy 2D seismic lines over the area outline the anticlinal structure, their quality is insufficient for quantitative interpretation. Earlier studies have shown that the natural gas stored in the Stenlille aquifer exhibits a seismic response similar to the modeled CO2 fluid in the Havnsø structure. Thus, seismic reservoir characterization carried out on the Stenlille aquifer gas storage in terms of identifying spatial distribution of gas and outlining faults would provide insight regarding value addition that seismic data can bring into the proposed CO2 storage at Havnsø. Using the available poststack seismic data, we apply an integrated reservoir characterization analysis. After performing the adequate data conditioning, the impedance of the target Stenlille Formation is estimated through generation of an accurate low-frequency model. Thereafter, multiattribute analysis was used to generate volumetric estimates of porosity, gamma ray, and water saturation within the target formation so that the spatial distribution of gas can be mapped. The resulting porosity and gamma-ray volumes indicate encouraging results and were used for Bayesian classification to predict the probability of the more important lithofacies, namely, sand, shale, moderate-porosity sand, and moderate-porosity shaly sand, which enabled the mapping of high-porosity/facies zones in the two aquifer storage levels. Independently, we make use of unsupervised machine learning applications for seismic facies prediction and compare them at the two storage levels, which will be presented in the part 2 of this paper.
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

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

Feminism, 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

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.
The Current Accuracy, Cost-Effectiveness, and Uses of Musculoskeletal Telehealth and Telerehabilitation Services
Authors: Rennie Katherine , Taylor Charles , Corriero Anna Chiara , Chong Collin , Sewell Edward , Hadley James , Ardani Shina
Published: July 2022

Musculoskeletal conditions are a major contributor to global morbidity. During the COVID-19 pandemic, clinicians needed to rapidly meet the evolving requirements of their patients, which resulted in an increased adoption of telehealth services. This area needs more research, as there is currently a paucity of studies, and telehealth practices are continuing to advance and evolve. This study subsequently aims to evaluate the ethics, health economics, and accuracy of current musculoskeletal telehealth services. This article combines three original studies; a telehealth accuracy systematic review; a cost-effectiveness scoping review; and a biopsychosocial narrative review. These studies were combined into one article. This article concludes that telehealth services achieve an average agreement with in-person assessments of 62% for the knee and 31% for the shoulder and that telerehabilitation services incur average cost savings per patient of £38.57 but that these savings are primarily a result of a reduced need to travel.
A simple approach for extending up to the ultra-relativistic limit the theory of a non-relativistic Fermi gas
Authors: Grave de Peralta Luis
Published: July 2022

Background: The theory of a Fermi gas constitutes a useful physical model with multiple applications from solid state to stellar physics. The theory of a non-relativistic Fermi gas is relatively simple when compared with the one for a relativistic Fermi gas. Therefore, it would be useful if a rigorous theory of a relativistic Fermi gas could be constructed like the theory of a non-relativistic Fermi gas.

Methods: Such a theory, for T > 0 K, is presented here. It is based on using a recently reported formula for the energies of a relativistic spin-0 particle in a three-dimensional infinite well. The Pauli exclusion principle is used for taking care of the fermion nature of the particles forming a Fermi gas.

Results: A unified description of a Fermi gas at low temperatures is presented. This description is valid from the non-relativistic to the ultra-relativistic limits. Moreover, it is simple. The theory follows the relatively simple approach often used for constructing the theory of a non-relativistic Fermi gas.   

Conclusions: The ultra-relativistic results reported here are often obtained using a different approach than the one used in this work. These results are not new, but they corroborate the correctness of the presented approach. In addition, the relative simplicity of the approach presented in this work allows for teaching the theory of a relativistic Fermi gas in introductory quantum mechanics courses.
High-risk human-caused pathogen exposure events from 1975-2016
Authors: Manheim David , Lewis Gregory
Published: July 2022

Biological agents and infectious pathogens have the potential to cause very significant harm, as the natural occurrence of disease and pandemics makes clear. As a way to better understand the risk of Global Catastrophic Biological Risks due to human activities, rather than natural sources, this paper reports on a dataset of 71 incidents involving either accidental or purposeful exposure to, or infection by, a highly infectious pathogenic agent.

There has been significant effort put into both reducing the risk of purposeful spread of biological weapons, and biosafety intended to prevent the exposure to, or release of, dangerous pathogens in the course of research. Despite these efforts, there are incidents of various types that could potentially be controlled or eliminated by different lab and/or bioweapon research choices and safety procedures.

The dataset of events presented here was compiled during a project conducted in 2019 to better understand biological risks from anthropic sources. The events which are listed are unrelated to clinical treatment of naturally occurring outbreaks, and are instead entirely the result of human decisions and mistakes. While the events cover a wide range of cases, the criteria used covers a variety of events previously scattered across academic, policy, and other unpublished or not generally available sources.
Bias from questionnaire invitation and response in COVID-19 research: an example using ALSPAC
Authors: Fernández-Sanlés Alba , Smith Daniel , Clayton Gemma L , Northstone Kate , Carter Alice R , Millard Louise AC , Borges Maria Carolina , Timpson Nicholas John , Tilling Kate , Griffith Gareth J , Lawlor Deborah A.
Published: July 2022

Background: Longitudinal studies are crucial for identifying potential risk factors for infection with, and consequences of, COVID-19, but relationships can be biased if they are associated with invitation and response to data collection. We describe factors relating to questionnaire invitation and response in COVID-19 questionnaire data collection in a multigenerational birth cohort (the Avon Longitudinal Study of Parents and Children, ALSPAC).

Methods: We analysed online questionnaires completed between the beginning of the pandemic and easing of the first UK lockdown by participants with valid email addresses who had not actively disengaged from the study. We assessed associations of pre-pandemic sociodemographic, behavioural, anthropometric and health-related factors with: i) being sent a questionnaire; ii) returning a questionnaire; and iii) item response (for specific questions). Analyses were conducted in three cohorts: the index children born in the early 1990s (now young adults; 41 variables assessed), their mothers (35 variables) and the mothers’ partners (27 variables).

Results: Of 14,849 young adults, 41% were sent a questionnaire, of whom 57% returned one. Item response was >95%. In this cohort, 78% of factors were associated with being sent a questionnaire, 56% with returning one, and, as an example of item response, 20% with keyworker status response. For instance, children from mothers educated to degree-level had greater odds of being sent a questionnaire (OR=5.59; 95% CI=4.87-6.41), returning one (OR=1.60; 95% CI=1.31-1.95), and responding to items (e.g., keyworker status OR=1.65; 95% CI=0.88-3.04), relative to children from mothers with fewer qualifications. Invitation and response rates and associations were similar in all cohorts.

Conclusions: These results highlight the importance of considering potential biases due to non-response when using longitudinal studies in COVID-19 research and interpreting results. We recommend researchers report response rates and factors associated with invitation and response in all COVID-19 observational research studies, which can inform sensitivity analyses.
Validation and clinical application of a method to quantify efavirenz in cervicovaginal secretions from flocked swabs using liquid chromatography tandem mass spectrometry
Authors: Olagunju Adeniyi , Nwogu Jacinta , Eniayewu Oluwasegun , Atoyebi Shakir , Amara Alieu , Kpamor John , Bolaji Oluseye , Adejuyigbe Ebunoluwa , Owen Andrew , Khoo Saye
Published: July 2022

Background : A liquid chromatography tandem mass spectrometry method to quantify drugs in dried cervicovaginal secretions from flocked swabs was developed and validated using the antiretroviral efavirenz as an example.

Methods: Cervicovaginal swabs (CVS) were prepared by submerging flocked swabs in efavirenz-spiked plasma matrix. Time to full saturation, weight uniformity, recovery and room temperature stability were evaluated. Chromatographic separation was on a reverse-phase C18 column by gradient elution using 1mM ammonium acetate in water/acetonitrile at 400 µL/min. Detection and quantification were on a TSQ Quantum Access triple quadrupole mass spectrometer operated in negative ionisation mode. The method was used to quantify efavirenz in CVS samples from human immunodeficiency virus (HIV)-positive women in the VADICT study (NCT03284645). A total of 98 samples (35 paired intensive CVS and DBS pharmacokinetic samples, 14 paired sparse CVS and DBS samples) from 19 participants were available for this analysis.

Results: Swabs were fully saturated within 15 seconds, absorbing 128 µL of plasma matrix with coefficient of variation (%CV) below 1.3%. The method was linear with a weighting factor (1/X) in the range of 25-10000 ng/mL with inter- and intra-day precision (% CV) of 7.69-14.9%, and accuracy (% bias) of 99.1-105.3%. Mean recovery of efavirenz from CVS was 83.8% (%CV, 11.2) with no significant matrix effect. Efavirenz remained stable in swabs for at least 35 days after drying and storage at room temperature. Median (range) CVS efavirenz AUC 0-24h was 16370 ng*h/mL (5803-22088), C max was 1618 ng/mL (610-2438) at a T max of 8.0 h (8.0-12), and C min was 399 ng/mL (110-981). Efavirenz CVS:plasma AUC 0-24h ratio was 0.41 (0.20-0.59).

Conclusions: Further application of this method will improve our understanding of the pharmacology of other therapeutics in the female genital tract, including in low- and middle-income countries.
Comparative analysis of potential broad-spectrum neuronal Cre drivers
Authors: Paton Katie M , Selfridge Jim , Guy Jacky , Bird Adrian
Published: July 2022

Cre/Lox technology is a powerful tool in the mouse genetics tool-box as it enables tissue-specific and inducible mutagenesis of specific gene loci. Correct interpretation of phenotypes depends upon knowledge of the Cre expression pattern in the chosen mouse driver line to ensure that appropriate cell types are targeted. For studies of the brain and neurological disease a pan-neuronal promoter that reliably drives efficient neuron-specific transgene expression would be valuable. Here we compare a widely used “pan-neuronal” mouse Cre driver line, Syn1-cre, with a little-known alternative, Snap25-IRES2-cre. Our results show that the Syn1-cre line broadly expresses in the brain but is indetectable in more than half of all neurons and weakly active in testes. In contrast the Snap25-IRES2-cre line expressed Cre in a high proportion of neurons (~85%) and was indetectable in all non-brain tissues that were analysed, including testes. Our findings suggest that for many purposes Snap25-IRES2-cre is superior to Syn1-cre as a potential pan-neuronal cre driver.
HEART RATE VARIABILITY DURING MENTAL AND PHYSICAL LOAD IN STUDENTS
Authors: Nikolaeva Tatyana M. , Golubeva Elena K. , Skorlupkin Dmitriy A. , Yarchenkova Larisa L.
Published: July 2022

The influence of physical and cognitive activity causes tension in the regulatory systems of the body, which leads to a change in heart rate variability. The aim of the work is a comparative investigation of the characteristics of heart rate variability during mental and physical activity in students. Determination of temporal and spectral indicators of heart rate variability was carried out using the APK “Poly-Spectrum” company “Neurosoft” (Ivanovo). To simulate the state of mental tension, the Bourdon-Anfimov correction test was used. When studying the effect of physical activity on heart rate indicators, the subject was asked to climb a step 25 cm high for 5 minutes. Two loads were used. The power of the first of them was 300 kg · m / min, the power of the second – 600 kg · m / min. The influence of cognitive and physical activity leads to the activation of the sympathetic link of the autonomic nervous system. The greatest deviation of heart rate indicators is exerted by a physical load with a capacity of 600 kg·m / min. The degree of change in the parameters of heart rate variability at a load of 300kg m / min practically does not differ from the results of the influence of cognitive load, indicating the same severity of the autonomic response.
SAFE FOOD FOR PATIENTS WITH PHENYLKETONURIA: AN INNOVATIVE METHOD OF PRODUCING PROTEIN-FREE PASTA PRODUCTS
Authors: Litvyak Vladimir V. , Bykova Svetlana T. , Roslyakov Yuri F. , Kuzina Lidia B.
Published: July 2022

Background. At the moment, there is only a little information about the formulations of protein-free food products. Therefore, developing innovative methods of obtaining protein-free pasta is relevant for medicine and dietetics.

The object of study. Phenylketonuria, pasta from native starches, extrusion starches, dried fruit puree, modified cellulose, gum, free amino acids, vitamins, minerals, salt.

Results. The article, for the first time, proposes an original method for the production of pasta with low protein content, including dough preparation, shaping, and drying, which differs from previously known ones in that starch (potato or corn, or tapioca, or rice, or wheat, or their mixtures of various ratios) extrusion modified, modified cellulose and gum: guar or xanthan, as an enriching additive are used: vitamins and vitamin-like substances: A or C, or B1, or B2, or B3, or B4, or B5, or B6, or B7 or B8 or B9 or B10 or B11 or B12 or Bs or B13 or B14 or B15 or D or E or H or H1 or P or K or N, or Q, or U, β-carotene, or mixtures thereof in various ratios, free amino acids: ala or gly, or val, or ser, or leu, or ile, or pro, or thr, or his, or met, or cys, or tyr, or trp, or asn, or asp, or gln, or glu, or arg, or lys, or mixtures thereof various ratios, minerals: Ca3(PO4)2 or MgO, or FeSO4, or ZnO, or CuSO4, or MnSO4, or Na2SeO3, or KI, or mixtures thereof in various ratios or dry puree from: apples or papayas, or pears, or persimmons, or pomegranate, or melon, or grapes, or mango, or figs, or radishes, or cashews, or pineapple, or tangerines, and as a food flavor – salt: sea, table or table iodized, as well as their mixtures of various ratios, are prepared kneading the dough with a total moisture content of the mixture of 35%, then molding is carried out at 60–85°C and drying at 25°C for 24 hours.

Conclusion. The following mixtures are the most optimal: 1) amino acids: ala, arg, asp, cys, gly, glu, his, ile, leu, met, pro, ser, thr, trp, tyr, val at a ratio of 1.8: 2: 6 .2 : 2.1 : 1 : 11.7 : 1.3 : 3.8 : 11.6 : 4.8 : 1.4 : 4.1 : 3.5 : 3.2 : 1.6 : 3 .7: 3.4; 2) vitamins and vitamin-like substances: A, D3, E, β-carotene, B1, B2, B3, B5, B6, B9, B12, B7, C at a ratio of 132.1 : 2.4 : 8095 : 57.1 : 50 : 71.4 : 476.2 : 595.2 : 23.8 : 11.9 : 1 : 1.7 : 9523.8; 3) minerals: Ca3(PO4)2, MgO, FeSO4, ZnO, CuSO4, MnSO4, Na2SeO3, KI at a ratio of 34000 : 3000 : 70 : 300 : 40 : 1000 : 1 : 7.
Pricing in Nonconvex Markets: How to Price Electricity in the Presence of Demand Response
Authors: Bichler Martin , Knörr Johannes , Maldonado Felipe
Published: July 2022

Climate change and the transition to renewable energy sources have had a significant impact on wholesale electricity markets. This has led to renewed interest in the design of electricity markets and pricing rules for spot markets. It is well known that theoretical ideals such as Walrasian equilibria cannot be obtained because of the nonconvex nature of the market-clearing problem. Instead, current pricing rules compute linear and anonymous price signals, yet at these prices, market participants often make a loss. Such losses are compensated by individual side payments that distort the price signal and have thus come under scrutiny by regulators. In this article, the authors examine this issue in greater detail. In markets with price-sensitive or flexible demand—which becomes increasingly important with growing levels of renewables—there can be no linear pricing rule that avoids make-whole payments under the welfare-maximizing allocation. Motivated by this observation, the authors introduce a pricing rule that minimizes make-whole payments and compare it against alternative pricing schemes. Numerical experiments indicate how the novel pricing rule can substantially reduce make-whole payments without significant impact on the overall market price. The findings provide input for the ongoing policy debate on make-whole payments in wholesale electricity markets.
New Afrotropical and Oriental elements in the weevil fauna of Iran (Coleoptera: Curculionidae) with discussion on their origin
Authors: YUNAKOV NIKOLAI , NASSERZADEH HIVA , REZAEI NASTARAN , ZARGHAMI SARA
Published: July 2022

Examination of Conocarpus erectus L., an adventive ornamental plant growing on Kish Island, revealed Myllocerus undecimpustulatus and Systates omanicus, both weevils new to Iran. Comparatively mesophilic Myllocerus undecimpustulatus is an invasive pest with origin from the Indian subcontinent, and is highly recommended for Internal Quarantine (A1) in Iran. Xerophilic Systates omanicus was thus far considered an endemic of eastern Arabia but likely it is also native to Kish Island. This finding is in line with hypothesis on Pleistocene colonization of Arabia and Persian Gulf region with subsequent speciation of Systates during African Humid Period occurring from the very beginning of Marine Isotope Stage 5.
Quality of Honey Produced by Four Species Of Stingless Bees in the Central Region of the State of Tocantins
Authors: Ribeiro Maisa Fernandes , Da Silva Roberta Zani , Domingos Rosilene Naves
Published: July 2022

Meliponiculture, the rational breeding of native stingless bees, is considered an excelente sustainable alternative to assist in the pollination process and is an economically viable activity. In the cerrado of Tocantins, the meliponine species that stand out most due to their wide distribution are: Scaptotrigona tubiba, Melipona fasciculata,M. rufiventris and Tetragonisca angustula. The bibliographic collection about these species is still little explored, hence there is a need for research to deepen the existing knowledge in the area. For this reason, the aim of this study was: a) to quantify the honey production of four meliponine species: T. angustula, M. fasciculata, M. rufiventris, and S. tubiba; b) to determine the physicochemical characteristics of the product; c) measure the biological parameters of the colony and d) evaluate the profile and sensory acceptance of honey in the municipalities, Palmas and Miracema, in the Tocantins. The study evaluated the biological parameters of the colony, honey production, and physicochemical analysis. The highest honey production came from the species T. angustula in the two collections for the municipality of Palmas. For Miracema, the species S. tubiba and M. fasciculata were evaluated, respectively. The physicochemical parameters evaluated fit the norms assigned to honey quality control. Results showed that honey from M. fasciculata was the sensory profile that obtained the best average among the characteristics observed in the study. There was a positive and negative correlation between the biological parameters, with a significant difference only between the characters’ height and diameter of the honey pot.
Inflammatory Aseptic Arthropathy in the Setting of COVID-19: A Case Report
Authors: Sharma Akhil , Savalia Krupa , Parekh Selene G.
Published: July 2022

Introduction: COVID-19 is among the most deleterious pandemics that the world has ever faced. It is known that SARS-CoV-2 engenders its effects by triggering a massive immune response identified as a “cytokine storm,” but the full extent of clinical manifestations of the disease is still not understood. Case Presentation:We report the first case of a patient with COVID-19 infection who developed inflammatory (IL) aseptic arthropathy. The patient is a South Asian male of Indian origin residing in the United States. Conclusion: This case demonstrates the importance of remaining vigilant about the new and unique manners, in which COVID-19 may present itself. Providers should be aware of the possible development of IL arthropathy in patients with the disease. Keywords: COVID-19, inflammatory arthropathy, aseptic arthropathy, musculoskeletal sequelae.
Surgical Treatment of Stage Four Knee Pressure Injury with Pedicled Fasciocutaneous Flap in Patient Affected by Spina Bifida – Case Report
Authors: Zingarelli Enrico M , Perrero Luca , Ghiglione Marco , Panizza Renzo
Published: July 2022

Introduction:Patients affected by spina bifida (SB) can present varying degrees of paralysis, limited mobility, impaired sensation, orthopedic problems and bowel, bladder, and renal impairments. Skin wounds are reported as one of the primary diagnosis associated with hospitalizations in SB affected patients. In young patients, pressure injuries can occur more frequently at the lower limb. A multidisciplinary approach and a proper surgical technique are mandatory to obtain favorable long-term outcomes, in terms of adequate coverage and risk of recurrence. Case Presentation:A Caucasian male 21-year-old wheelchair-bound patient with history of SB was admitted to our department with stage four pressure injury on the medial aspect of knee joint and osteomyelitis. After antibiotic therapy wound preparation and debridement, we covered the pressure sore with a pedicled fasciocutaneous flap harvested from the medial compartment of the thigh. In the distal part, we splitted the fascia from the flap and used it to reconstruct the exposed knee joint. We did not report any complications and no recurrence was observed at 1-year follow-up examination. Conclusion:In this reported case, the multidisciplinary approach and the surgical technique allowed us to cover the soft-tissue defect around knee joint, reducing morbidity, surgical time, and cost with good long-term outcomes. Keywords:Spina bifida, pressure injuries, fasciocutaneous flap.