bluuebunny/crossref_metadata_2025 huggingface dataset:
Rationale for the design and technological parameters of the extruder for the production of sapropel and grain feed
Authors: Morozov V V , Bogdanov K A , Smelik V A , Volkhonov M S , Kukhar V S
Published: March 2021

It is reasonable to use extruded sapropelesern feed for increasing the productivity of farm animals. This feed supplements the animal’s body with minerals and vitamins as well as has good digestibility. It is well stored and has a low cost. The article shows the scheme of the extruder developed by the authors. It allows to prepare sapropel and grain feed. For the aim of being able to specify the necessary technological parameters of the extruder operation at the design stage, analytical dependences were deduced to determine the processing temperature of the mixture, extruder capacity and the power spent on the extrusion process. The mathematical dependences received theoretically were tested experimentally, and the maximum error does not outweigh 5%, corresponding to the required accuracy of the modelling. The article also determines the most rational modes of extruder operation.
Exploring few and single layer CrPS4 with near-field infrared spectroscopy
Authors: Neal Sabine N , O’Neal Kenneth R , Haglund Amanda V , Mandrus David G , Bechtel Hans A , Carr G Lawrence , Haule Kristjan , Vanderbilt David , Kim Heung-Sik , Musfeldt Janice L
Published: March 2021

We combine synchrotron-based near-field infrared spectroscopy and first principles lattice dynamics calculations to explore the vibrational response of CrPS4 in bulk, few-, and single-layer form. Analysis of the mode pattern reveals a C2 polar + chiral space group, no symmetry crossover as a function of layer number, and a series of non-monotonic frequency shifts in which modes with significant intralayer character harden on approach to the ultra-thin limit whereas those containing interlayer motion or more complicated displacement patterns soften and show inflection points or steps. This is different from MnPS3 where phonons shift as 1/size2 and are sensitive to the three-fold rotation about the metal center that drives the symmetry crossover. We discuss these differences as well as implications for properties such as electric polarization in terms of presence or absence of the P–P dimer and other aspects of local structure, sheet density, and size of the van der Waals gap.
Study on toughening mechanism of Ti on weld metal of high strength steel
Authors: Han Xu , Liu Zhengjun , Wu Dan , Liang Xuewei
Published: March 2021

The effect of Ti element on acicular ferrite microstructure of high strength steel weld was studied by scanning electron microscope(SEM), Transmission electron microscopy(TEM) and EDX spectrum analysis. The results show that Ti element content in a certain range can promote the precipitation of acicular ferrite in high strength steel weld metal. The increase of Ti content in the weld makes the Ti-rich inclusions increase, which is conducive to the formation of acicular ferrite. Charpy impact test results show that with the increase of Ti content, the impact toughness of weld metal increases first and then decreases. The tensile test results show that the tensile strength of weld metal increases and the elongation decreases with the increase of Ti content. There are high density dislocations and M-A components in acicular ferrite. M-A elements hinder the crack growth and improve the impact toughness of weld metal. When the Ti content is 0.253%, the impact energy of the weld metal is 155 J at-60 °C, and the impact toughness is the best.
Tuning the thickness of graphitic nanofilms for wurtzite materials by vertical weak electric field under a certain pressure
Authors: Li Yan-Li , Hu Sanlue , Zheng Guang
Published: March 2021

Theoretical and experimental results indicate that naturally the ultrathin nanofilms of some wurtzite (WZ) semiconductors will transform into a stable nonpolar graphitelike structure from the polar surface. Normally, the thicknesses are just limited to a few atomic layers. By epitaxial tensile strain, the thickness can be extended. In this work, employing the first-principles calculations focus on WZ materials ZnO, BeO, SiC, GaN, InN and AlN, we predicted that under a certain pressure with a weak electric field, their thickness range of forming graphitic nanofilms is greatly enlarged. This research provides theoretical guidance for the synthesis of new two-dimensional (2D) structures.
Planning Organization
Authors: Bowes Ashley
Published: March 2021

From its very beginning in 1909, planning legislation has given to local authorities direct power and responsibility for the carrying on of the day-to-day administration of land-use control. Central government’s role in the administration of planning began as, and has since remained, the supervision and co-ordination of the way in which those powers and responsibilities are exercised.
The Need for Planning Permission 1: General Permitted Development Order; Local Development Orders
Authors: Bowes Ashley
Published: March 2021

Section 57(1) of the 1990 Act provides that, subject to the provisions of the section, planning permission is required for the carrying out of any development of land. Planning permission may be granted in three main ways, namely by development order without the need for any application to be made, by a deemed grant of planning permission, or as the result of an express application for planning permission made to the local planning authority.
Practical Considerations and Testing Nuances for the Detection of Lupus Anticoagulant: Do Low Phospholipid Screen Results, Assay Type, and Test Ratio Matter?
Authors: Asakrah Saja , Davis Roger , Bhargava Parul
Published: March 2021

Objectives

Lupus anticoagulant (LA) detection requires (1) prolongation of a phospholipid (PL)–dependent clot-based screening assay, (2) noncorrection upon adding normal pooled plasma, and (3) a confirmatory PL dependency test. Paired LA assays run screening and confirmatory tests simultaneously, with their test ratio (TR) or differences used to evaluate test results. We evaluated patients whose paired testing demonstrated PL dependence suggestive of LA, yet the low PL screen was not prolonged.

Methods

Clinical and laboratory parameters are compared across (1) true positive (screen prolonged, TR positive) vs borderline (screen not prolonged, TR positive); (2) low-, moderate-, and high-TR subgroups; and (3) dilute Russell viper venom time (dRVVT) vs silica clotting time (SCT).

Results

Borderline samples are not statistically different from true positives in their rate of repeat LA positivity or association with other anti-PL antibodies. Compared with true positives, borderline dRVVT is more frequent in pregnancy, women, and younger age. Elevated activated partial thromboplastin time is more frequent in true-positive dRVVT and SCT vs borderline and with an increasing dRVVT TR. LA persistence is more frequent with an increasing SCT TR. In addition, dRVVT true positivity is more frequent with thromboembolic events, while SCT is more frequent with autoimmunity and pregnancy complications.

Conclusions

Negative low-PL screens may not necessarily lack LA. A reevaluation of the laboratory criteria for LA detection may be needed.
Impact of pharmacist-led selective audit and feedback on outpatient antibiotic prescribing for UTIs and SSTIs
Authors: Choi Patricia W , Benzer Jessica A , Coon Joel , Egwuatu Nnaemeka E , Dumkow Lisa E
Published: March 2021

Purpose

An estimated 30% of all outpatient antibiotic prescriptions in the United States are unnecessary. The Joint Commission, in 2016, implemented core elements of performance requiring antimicrobial stewardship programs (ASPs) to expand to outpatient practice settings. A study was conducted to determine whether pharmacist-led audit and feedback would improve antibiotic prescribing for urinary tract infections (UTIs) and skin and soft tissue infection (SSTIs) at 2 primary care practices.

Methods

A retrospective, quasi-experimental study was conducted to evaluate antibiotic prescribing for patients treated for a UTI or SSTI at 2 primary care offices (a family medicine office and an internal medicine office). The primary objective was to compare the rate of appropriate antibiotic prescribing to patients treated before implementation of a pharmacist-led audit-and-feedback process for reviewing antibiotics prescribed for UTIs and SSTIs (the pre-ASP group) and patients treated after process implementation (the post-ASP group). Total regimen appropriateness was defined by appropriate antibiotic selection, dose, duration, and therapy indication in accordance with institutional outpatient empiric therapy guidelines. Secondary objectives included comparing rates of infection-related revisits and Clostridioides difficile infection between groups.

Results

A total of 400 patients were included in the study (pre-ASP group, n = 200; post-ASP group, n = 200). The rate of total antibiotic prescribing appropriateness improved significantly, from 27.5% to 50.5% (P < 0.0001), after implementation of the audit-and-feedback process. There were also significant improvements in the post-ASP group vs the pre-ASP period in the individual components of regimen appropriateness: appropriate drug (70% vs 53%, P < 0.001), appropriate duration (83.5% vs 57.5%, P < 0.001), and appropriate therapy indication (98% vs 94%, P = 0.041). There were no significant between-group differences in other outcomes such as rates of adverse events, treatment failure, C. difficile infection, and infection-related revisits or hospitalizations within 30 days.

Conclusion

A pharmacist-led audit-and-feedback outpatient stewardship strategy was demonstrated to achieve significant improvement in outpatient antibiotic prescribing for UTI and SSTI.
Insights into the evolutionary forces that shape the codon usage in the viral genome segments encoding intrinsically disordered protein regions
Authors: Kumar Naveen , Kaushik Rahul , Tennakoon Chandana , Uversky Vladimir N , Longhi Sonia , Zhang Kam Y J , Bhatia Sandeep
Published: March 2021

Intrinsically disordered regions/proteins (IDRs) are abundant across all the domains of life, where they perform important regulatory roles and supplement the biological functions of structured proteins/regions (SRs). Despite the multifunctionality features of IDRs, several interrogations on the evolution of viral genomic regions encoding IDRs in diverse viral proteins remain unreciprocated. To fill this gap, we benchmarked the findings of two most widely used and reliable intrinsic disorder prediction algorithms (IUPred2A and ESpritz) to a dataset of 6108 reference viral proteomes to unravel the multifaceted evolutionary forces that shape the codon usage in the viral genomic regions encoding for IDRs and SRs. We found persuasive evidence that the natural selection predominantly governs the evolution of codon usage in regions encoding IDRs by most of the viruses. In addition, we confirm not only that codon usage in regions encoding IDRs is less optimized for the protein synthesis machinery (transfer RNAs pool) of their host than for those encoding SRs, but also that the selective constraints imposed by codon bias sustain this reduced optimization in IDRs. Our analysis also establishes that IDRs in viruses are likely to tolerate more translational errors than SRs. All these findings hold true, irrespective of the disorder prediction algorithms used to classify IDRs. In conclusion, our study offers a novel perspective on the evolution of viral IDRs and the evolutionary adaptability to multiple taxonomically divergent hosts.
MaveRegistry: a collaboration platform for multiplexed assays of variant effect
Authors: Kuang Da , Weile Jochen , Kishore Nishka , Nguyen Maria , Rubin Alan F , Fields Stanley , Fowler Douglas M , Roth Frederick P
Published: March 2021

Multiplexed assays of variant effect (MAVEs) are capable of experimentally testing all possible single nucleotide or amino acid variants in selected genomic regions, generating ‘variant effect maps’, which provide biochemical insight and functional evidence to enable more rapid and accurate clinical interpretation of human variation. Because the international community applying MAVE approaches is growing rapidly, we developed the online MaveRegistry platform to catalyze collaboration, reduce redundant efforts, allow stakeholders to nominate targets and enable tracking and sharing of progress on ongoing MAVE projects.

Availability and implementation

MaveRegistry service: https://registry.varianteffect.org. MaveRegistry source code: https://github.com/kvnkuang/maveregistry-front-end.
Insights into the lipidome and primary metabolome of the uterus from day 14 cyclic and pregnant sheep
Authors: O’Neil Eleanore V , Spencer Thomas E
Published: March 2021

In ruminants, conceptus elongation requires the endometrium and its secretions. The amino acid, carbohydrate, and protein composition of the uterine lumen during early pregnancy has been defined in sheep; however, a comprehensive understanding of metabolomic changes in the uterine lumen is lacking, particularly with respect to lipids. Here, the lipidome and primary metabolome of the uterine lumen, endometrium, and/or conceptus was determined on day 14 of the estrous cycle and pregnancy. Lipid droplets and select triglycerides were depleted in the endometrium of pregnant ewes. In contrast, select ceramides, diglycerides, and non-esterified fatty acids as well as several phospholipid classes (phosphatidylcholine, phosphatidylinositol, phosphatidylglycerols, and diacylglycerols) were elevated in the uterine lumen of pregnant ewes. Lipidomic analysis of the conceptus revealed that triglycerides are particularly abundant within the conceptus. Primary metabolite analyses found elevated amino acids, carbohydrates, and energy substrates, among others, in the uterine lumen of pregnant ewes. Collectively, this study supports the hypothesis that lipids are important components of the uterine lumen that govern conceptus elongation and growth during early pregnancy.
Single-index models with functional connectivity network predictors
Authors: Weaver Caleb , Xiao Luo , Lindquist Martin A
Published: March 2021

Functional connectivity is defined as the undirected association between two or more functional magnetic resonance imaging (fMRI) time series. Increasingly, subject-level functional connectivity data have been used to predict and classify clinical outcomes and subject attributes. We propose a single-index model wherein response variables and sparse functional connectivity network valued predictors are linked by an unspecified smooth function in order to accommodate potentially nonlinear relationships. We exploit the network structure of functional connectivity by imposing meaningful sparsity constraints, which lead not only to the identification of association of interactions between regions with the response but also the assessment of whether or not the functional connectivity associated with a brain region is related to the response variable. We demonstrate the effectiveness of the proposed model in simulation studies and in an application to a resting-state fMRI data set from the Human Connectome Project to model fluid intelligence and sex and to identify predictive links between brain regions.
Self-Face Activates the Dopamine Reward Pathway without Awareness
Authors: Ota Chisa , Nakano Tamami
Published: March 2021

The self-face advantage has been demonstrated not only at the supraliminal level, but also at the subliminal level. However, it remains unclear whether subliminal self-face processing involves the same neural networks as those for supraliminal self-face processing. Here, we show that the ventral tegmental area, a center of the dopamine reward pathway, exhibited greater activation to subliminal presentations of the self-face than those of the others’ faces, whereas subliminal presentations of the others’ faces induced activation in the amygdala, which generally responds to unfamiliar information. This self-other difference in brain response was consistently observed even when the facial configuration was modified without changing the shape of the facial parts. The present findings suggest that the dopamine reward pathway is involved in automatic self-advantage in face processing, and the subliminal self-other facial discrimination does not depend on information of the precise facial configuration.
Comparison of Blood (1–>3)-β-d-Glucan Levels in AIDS-Related Pneumocystis jirovecii Pneumonia and AIDS-Related Progressive Disseminated Histoplasmosis
Authors: Saccente Michael , Krishnan Gayathri
Published: March 2021

In this retrospective study, (1–>3)-β-d-glucan (B-glucan) was an unreliable marker for AIDS-related Pneumocystis jirovecii pneumonia (PCP) because a high percentage of participants with progressive disseminated histoplasmosis and respiratory symptoms had a positive B-glucan result. Where histoplasmosis is common, attributing B-glucan positivity to PCP without further testing risks misdiagnosis.
Plant Volatiles and Oviposition Behavior in the Selection of Barley Cultivars by Wheat Stem Sawfly (Hymenoptera: Cephidae)
Authors: Achhami Buddhi B , Reddy Gadi V P , Hofland M L , Sherman Jamie D , Peterson Robert K D , Weaver David K
Published: March 2021

Wheat stem sawfly, [Cephus cinctus (Hymenoptera: Cephidae)], females display complex behaviors for host selection and oviposition. Susceptible hollow stem wheat (Triticum aestivum L.) cultivars release a greater amount of attractive compound, (Z)-3-hexenyl acetate and receive a greater number of eggs compared to resistant solid stem wheat cultivars. However, barley (Hordeum vulgare L.) is becoming a more common host for C. cinctus in Montana. Therefore, how do host selection and oviposition behaviors on barley cultivars compare to what happens when encountering wheat cultivars? To answer this question, we carried out greenhouse experiments using two barley cultivars: ‘Hockett’ and ‘Craft’. Between these cultivars at Zadoks stages 34 and 49, we compared host selection decisions using a Y-tube olfactometer, compared oviposition behaviors on stems, and counted the number of eggs inside individual stems. In Y-tube bioassays, we found a greater number of C. cinctus females were attracted to the airstream passing over ‘Hockett’ than ‘Craft’ barley cultivars. Although the frequencies of oviposition behaviors were similar between these cultivars, the number of eggs was greater in ‘Hockett’. Volatile profiles indicated that the amount of linalool was greater in the airstream from ‘Craft’ than in ‘Hockett’ at Zadoks 34 while the amount of (Z)-3-hexenyl acetate was greater in airstream from ‘Hockett’ at both Zadoks 34 and 49. These results suggest that volatiles of barley plants influenced host selection behavior of ovipositing C. cinctus females, while other discriminating behaviors do not differ between cultivars.
Landscape Context Influences the Bee Conservation Value of Wildflower Plantings
Authors: McCullough Christopher T , Angelella Gina M , O’Rourke Megan E
Published: March 2021

Pollination provided by bees is a critical ecosystem service for agricultural production. However, bee populations are at risk from stressors such as habitat loss, pesticides, and disease. On-farm wildflower plantings is one mitigation strategy to provide habitat and resources for bees. In many instances, government programs can subsidize the installation of these plantings for private landowners. Semi-natural habitat (SNH) in the landscape is also important for bee conservation and may alter the effectiveness of wildflower plantings. In this study, we tested the effectiveness of wildflower plantings and interactions with SNH in the landscape for promoting bee abundance and richness. Bee surveys were conducted over 2 yr at 22 sites in eastern Virginia and Maryland. Wildflower plantings, averaging 0.22 ha in size, were installed and maintained by cooperators at 10 of the sites. In total, 5,122 bees were identified from 85 species. Wildflower plantings did not alter bee communities independently, but bee abundance was greater on farms with plantings and 20–30% SNH in the landscape. Bee abundance and richness had nonlinear responses to increasing SNH in the landscape. The positive effects for richness and abundance peaked when SNH was approximately 40% of the landscape. Similar to predictions of the intermediate-landscape complexity hypothesis, increases in bee abundance at wildflower sites were only detected in simplified landscapes. Results indicate that small wildflower plantings in the Mid-Atlantic U.S. only provided conservation benefits to bee communities under specific circumstances on the scale studied, and that conserving SNH across the landscape may be a more important strategy.
Appointing a Poet Laureate: National and Poetic Identities in 1813
Authors: Shipp Leo
Published: March 2021

Following the death of the incumbent Henry James Pye in 1813, the office of poet laureate came under scrutiny from press, court and government figures alike, and was eventually bestowed upon Robert Southey, having first been turned down by Walter Scott. This article examines the selection process and questions why, after a century in which the reputation of the office had fallen so far, it provoked such concern in 1813, and was suddenly thought an appropriate office for such pre-eminent ‘geniuses’ as Scott and Southey. Situating the selection process in the context of recent scholarship on national identity, cultural production and public opinion, it will be argued that the laureateship in 1813 can give us a unique and illuminating perspective on ideas of Britishness, patriotism and literature at the start of the nineteenth century, and of the place of court and public with regards to these ideas. In particular, the case of the laureateship demonstrates the variety, contingency and usability of notions of Britishness during the Napoleonic Wars: the ways that different agents invoked and thereby fashioned competing national identities in accordance with the needs of their discursive contexts. One possible constellation of Britishness, which came to the fore in the Liverpool ministry’s prosecution of the war effort and in the contest between the Edinburgh and Quarterly Reviews, validated ‘traditional’ forms of cultural production and patriotism in which court—and laureateship—played a crucial part.
The dynamics of picocyanobacteria from a hypereutrophic shallow lake is affected by light-climate and small-bodied zooplankton: a 10-year cytometric time-series analysis
Authors: Quiroga María Victoria , Huber Paula , Ospina-Serna Juliana , Diovisalvi Nadia , Odriozola Mariana , Cueto Gerardo R , Lagomarsino Leonardo , Fermani Paulina , Bustingorry José , Escaray Roberto , Zagarese Horacio , Unrein Fernando
Published: March 2021

In aquatic systems, an interplay between bottom-up and top-down processes determines the dynamic of picocyanobacteria (Pcy) abundance and community structure. Here, we analyzed a 10-year time series (sampled fortnightly) from a hypereutrophic turbid shallow lake located within the Pampa Region of South America, generating the first long-term record of freshwater Pcy from the Southern Hemisphere. We used a cytometric approach to study Pcy community, and focused on its relations with nutrient and light conditions (bottom-up) and potential grazers (top-down). A novel Pcy abundance seasonality with winter maximums was observed for years with relatively stable hydrological levels, related with decreased abundance of seasonal rotifers during colder seasons. Pcy showed lower abundance and higher cytometric alpha diversity during summer, probably due to a strong predation exerted by rotifers. In turn, a direct effect of the non-seasonal small cladocerans Bosmina spp. decreased Pcy abundance and induced a shift from single-cell Pcy into aggregated forms. This structuring effect of Bosmina spp. was further confirmed by Pcy cytometric (dis)similarity analyses from the time series and in situ experimental data. Remarkably, Pcy showed acclimatization to underwater light variations, resembling the relevance of light in this turbid system.
The Use of Readily Available Longitudinal Data to Predict the Likelihood of Surgery in Crohn Disease
Authors: Stidham Ryan W , Liu Yumu , Enchakalody Binu , Van Tony , Krishnamurthy Venkataramu , Su Grace L , Zhu Ji , Waljee Akbar K
Published: March 2021

Background

Although imaging, endoscopy, and inflammatory biomarkers are associated with future Crohn disease (CD) outcomes, common laboratory studies may also provide prognostic opportunities. We evaluated machine learning models incorporating routinely collected laboratory studies to predict surgical outcomes in U.S. Veterans with CD.

Methods

Adults with CD from a Veterans Health Administration, Veterans Integrated Service Networks (VISN) 10 cohort examined between 2001 and 2015 were used for analysis. Patient demographics, medication use, and longitudinal laboratory values were used to model future surgical outcomes within 1 year. Specifically, data at the time of prediction combined with historical laboratory data characteristics, described as slope, distribution statistics, fluctuation, and linear trend of laboratory values, were considered and principal component analysis transformations were performed to reduce the dimensionality. Lasso regularized logistic regression was used to select features and construct prediction models, with performance assessed by area under the receiver operating characteristic using 10-fold cross-validation.

Results

We included 4950 observations from 2809 unique patients, among whom 256 had surgery, for modeling. Our optimized model achieved a mean area under the receiver operating characteristic of 0.78 (SD, 0.002). Anti-tumor necrosis factor use was associated with a lower probability of surgery within 1 year and was the most influential predictor in the model, and corticosteroid use was associated with a higher probability of surgery. Among the laboratory variables, high platelet counts, high mean cell hemoglobin concentrations, low albumin levels, and low blood urea nitrogen values were identified as having an elevated influence and association with future surgery.

Conclusions

Using machine learning methods that incorporate current and historical data can predict the future risk of CD surgery.
A Bayesian approach to comparing common models of life-course epidemiology
Authors: Chumbley Justin , Xu Wenjia , Potente Cecilia , Harris Kathleen M , Shanahan Michael
Published: March 2021

Background

Life-course epidemiology studies people’s health over long periods, treating repeated measures of their experiences (usually risk factors) as predictors or causes of subsequent morbidity and mortality. Three hypotheses or models often guide the analyst in assessing these sequential risks: the accumulation model (all measurement occasions are equally important for predicting the outcome), the critical period model (only one occasion is important) and the sensitive periods model (a catch-all model for any other pattern of temporal dependence).

Methods

We propose a Bayesian omnibus test of these three composite models, as well as post hoc decompositions that identify their best respective sub-models. We test the approach via simulations, before presenting an empirical example that relates five sequential measurements of body weight to an RNAseq measure of colorectal-cancer disposition.

Results

The approach correctly identifies the life-course model under which the data were simulated. Our empirical cohort study indicated with >90% probability that colorectal-cancer disposition reflected a sensitive process, with current weight being most important but prior body weight also playing a role.

Conclusions

The Bayesian methods we present allow precise inferences about the probability of life-course models given the data and are applicable in realistic scenarios involving causal analysis and missing data.
Assessing pharmacists’ knowledge and compliance with narcotic inventory management using a computer-based educational platform
Authors: Hussein Rand , Killeen Rosemary , He Zhoushanyue , Grindrod Kelly
Published: March 2021

Objectives

Pharmacy professionals are required to take all necessary steps to protect commonly misused drugs such as opioids at their pharmacies to minimize the risk of diversion. The aim of this study is to assess Canadian pharmacy professionals’ knowledge and compliance with federal and provincial regulations using the computer-based educational platform Pharmacy5in5.

Methods

A Narcotic Inventory module was created and reviewed by experts representing provincial and federal regulators. Descriptive statistics were used to analyze users’ performance in quizzes. Binomial regression and logistic regression models were used to investigate the effect of demographic factors on users’ performance. P-values less than 0.05 were considered statistically significant.

Key findings

The analysis included data collected over a period of three months. A total of 792 users accessed the Narcotic Inventory module on the Pharmacy5in5 website between July 2019 and November 2019. Most of the users were licenced pharmacists (64%), female (72%), received their training in Canada (68%), and were practising in Ontario (80%). Users performed best on the quiz addressing the steps for reconciliation of inventory (93%), and worst on the quiz reviewing how to prepare for a Health Canada visit (66%).

Conclusions

Overall, pharmacy professionals showed adequate knowledge of the CDSA and provincial/territorial regulations regarding opioids inventory management. Conversely, the study highlighted poor compliance with the reporting of losses and theft of controlled substances by pharmacy professionals. Innovative approaches are needed to influence pharmacy professionals’ behaviours to improve their compliance with best practices concerning inventory management to reduce drug diversion.
Marmoset Metabolism, Nutrition, and Obesity
Authors: Ross Corinna N , Colman Ricki , Power Michael , Tardif Suzette
Published: March 2021

The use of marmosets as nonhuman primate models of human disease has undergone rapid expansion in the United States in the last decade, with an emphasis in the field of neuroscience. With this expanding need, there has been an increase in the formation of small marmoset colonies. The standardization in care and husbandry techniques for marmosets has historically lagged behind other established nonhuman primate models, resulting in a great deal of variation in practices between colonies. There remains a lack of consensus and evidence-based recommendations regarding best standards for nutrition, enrichment, weight management, and diagnostics for clinical metabolic disease. Marmoset base diets vary broadly in their nutritional value, and therefore the physiological responses to these diets also vary broadly. In this review, we briefly outline what is known about nutrition for captive marmosets and highlight what is known regarding metabolic dysfunction and obesity.
Endotoxin Acts Synergistically WithClostridioides difficileToxin B to Increase Interleukin 1β Production: A Potential Role for the Intestinal Biome in Modifying the Severity ofC. difficileColitis
Authors: Htwe Pyae , Aung Htay , Kywe Bohm , Niang Phyu T , Oo Thar Sann , Monhandas Sindhu , Kelly Libusha , Goldman David L
Published: March 2021

Background

Inflammation is a crucial driver of host damage in patients with Clostridioides difficile colitis. We examined the potential for the intestinal microbiome to modify inflammation in patients with C. difficile colitis via the effects of gut-derived endotoxin on cytokine production.

Methods

Endotoxin from Escherichia coli and Pseudomonas aeruginosa as well as stool-derived endotoxin were tested for their ability to enhance interleukin 1β (IL-1β) and tumor necrosis factor alpha (TNF-α) production by toxin B–stimulated peripheral blood mononuclear cells. Inflammasome and Toll-like receptor 4 (TLR4) blocking studies were done to discern the importance of these pathways, while metagenomic studies were done to characterize predominant organisms from stool samples.

Results

Endotoxin significantly enhanced the ability of C. difficile toxin B to promote IL-1β production but not TNF-α. The magnitude of this effect varied by endotoxin type and was dependent on combined inflammasome and TLR4 activation. Stool-derived endotoxin exhibited a similar synergistic effect on IL-1β production with less synergy observed for stools that contained a high proportion of γ-proteobacteria.

Conclusions

The ability of endotoxin to enhance IL-1β production highlights a manner by which the microbiome can modify inflammation and severity of C. difficile disease. This information may be useful in devising new therapies for severe C. difficile colitis.
Establishment of Deep-Eutectic-Solvent-Assisted Matrix Solid-Phase Dispersion Extraction for the Determination of Four Flavonoids in Scutellariae Radix Based on the Concept of Quality by Design
Authors: Yang Fei , Jiang Luyi , Mao Hui , Zou, and Yanfang , Chu Chu
Published: March 2021

Background

Sample preparation is the most crucial step in analytical schemes. Micro-matrix solid-phase dispersion, as a method for microextraction of analytes, has prevailed recently for its low sample and extraction solvent consumption. However, small amounts of adsorbent or sample, or a short extraction time, always bring uncertainty to the result when using this method.

Objective

The aim was to develop a simple and reliable method of deep-eutectic-solvent-assisted ultrasonic-synchronized matrix solid-phase dispersion microextraction for the analysis of four flavonoids in Scutellariae Radix based on the concept of quality by design.

Method

The ZSM-5 molecular sieve was used as a new adsorbent in the micro-matrix solid-phase dispersion process. Single-factor and Box–Behnken designs were used to construct the design space.

Results

Verification of the experiment demonstrated that the design space is robust. Under optimal conditions, all analytes showed good linearity (R2 > 0.999), high reproducibility (RSD < 2.24%) and stability (RSD < 2.87%), and satisfactory recoveries (95.90–102.31%), which indicated that the established method is reliable and reproducible. Moreover, it has been successfully applied to determine the flavonoids in nine batches of Scutellariae Radix.

Conclusions

The results indicate a great potential for analyzing complicated samples especially with small amount and helping to promote the quality control of the sample preparation process for traditional Chinese medicines.

Highlights

A systematic approach using a facile deep-eutectic-solvent-assisted ultrasonic-synchronized matrix solid-phase dispersion extraction coupled with HPLC for the analysis of flavonoids in Scutellariae Radix has been developed based on the concept of quality by design.
High-level expression of human CH2 domain from the Fc region in Pichia pastoris and preparation of anti-CH2 antibodies
Authors: Oyama Kosuke , Ohkuri Takatoshi , Inoue Mao , Caaveiro Jose M M , Ueda Tadashi
Published: March 2021

Pichia pastoris is a popular eukaryotic system employed for the fast, simple and inexpensive production of recombinant protein including biotherapeutics such as human albumin. The CH2 domain of human Immunoglobulin G (IgG) is a promising scaffold for developing novel therapeutics. To accelerate the research of CH2 domain, we have established a procedure to highly express human CH2 domain (∼150 mg/l) as well as human Fc (∼30 mg/l) in yeast P. pastoris. The procedure yields, simultaneously, a major glycosylated (∼70%) and non-glycosylated (∼30%) fractions. They can be easily separated with high purity. Although both forms of CH2 domain have essentially the same secondary structure, the presence of the glycan increased the thermal stability of the CH2 domain by about 5°C as determined from calorimetry. The purified glycosylated CH2 domain elicited polyclonal antibodies in mouse, recognizing not only the CH2 domain, but also recombinant human Fc and the commercial IgG1 antibody Rituxan. Protein A and Protein G binding to the kink region between CH2 domain and CH3 domain of human Fc are used to purify therapeutic proteins. Therefore, these antibodies are candidates to develop a novel affinity material to purify human antibodies using their CH2 domain.
#76: Epidemiology of Cytomegalovirus (CMV) in Pediatric Solid-Organ Transplant Recipients (SOTR) at Texas Children’s Hospital (TCH)
Authors: Valencia Deray K , Hosek K , Moulton E , Munoz F , Demmler-Harrison G , Bocchini C
Published: March 2021

Background

Despite the widespread use of prevention strategies, CMV remains a common opportunistic infection in SOTR. Contemporary data regarding CMV in pediatric SOTR are limited. We sought to determine the frequency of and risk factors for CMV infection and disease in a large single-center cohort of pediatric SOTR.

Methods

A retrospective cohort study of patients <22 years of age who received lung, heart, liver, kidney, or multi-organ transplants at TCH between 2010 and 2018 was completed. Universal CMV prophylaxis was used based on risk status (Figure 1). The primary outcome was quantifiable CMV DNAemia. Associations with CMV DNAemia were measured using Fisher exact, Kruskal–Wallis, and multivariate logistic regression. Survival analysis and time to CMV infection were assessed using Kaplan–Meier plots.

Results

Among 788 SOTR, 132 (17%) had quantifiable CMV DNAemia; this included 20/105 (19%) lung, 69/290 (24%) liver, 28/178 (16%) heart, 2/15 (13%) multi-organ, and 13/200 (7%) kidney recipients. Fifty-one (6%) SOTR had CMV DNAemia while on antiviral prophylaxis. Post-prophylaxis, 69 (9%) SOTR had CMV reactivation and 12 (2%) had primary infection. The median time to quantifiable DNAemia for patients that developed CMV was 290 days post-transplant for lung, 162 for liver, 186 for heart, and 294 for kidney (P < 0.01), reflecting differences in prophylaxis strategies. High-risk CMV status (D+/R– for heart, liver, kidney, and D+ and/or R+ for lung) was associated with CMV DNAemia (P < 0.01). Type of organ transplanted also showed an association with CMV DNAemia (P = 0.02) with liver transplant recipients more being more likely to have a positive CMV PCR. DNAemia was not associated with age at transplantation, type of organ, or the use of induction immunosuppression. There was no difference in survival during the study follow-up period (1–9 yr) for SOTR with vs. without DNAemia (P = 0.48). Overall, 22/788 (3%) SOTR had CMV disease, 3 (3%) lung, 4 (2%) heart, 8 (3%) liver, 1 (6%) multi-organ, and 6 (3%) kidney recipients. Twenty had CMV syndrome and 2 had tissue invasive disease. Median (range) maximum viral loads were 27700 IU/mL (233-3912694) for SOTR with vs. 900 IU/mL (26-112000) for SOTR without CMV disease (P < 0.01).

Conclusion

This large contemporary cohort of pediatric SOTR on universal prophylaxis demonstrates low overall rates of CMV DNAemia and CMV disease. High-risk CMV status remains associated with CMV DNAemia, suggesting that further interventions targeting this group may be warranted.
#65: Characterization of Resistance Patterns Among Isolates of E. coli and Klebsiella sp. from Wastewater, and Clinical Samples in a Tertiary Care Children’s Hospital in Lima, Peru
Authors: Santillán Carlos F , Tsukayama Pablo , Calderón Maritza , Castillo Camila , Huancachoque Janet
Published: March 2021

Background

Environmental monitoring of enterobacteria in hospital wastewater could be a useful tool to understand the composition of the microbiota in patients, their visits, and healthcare personnel, but it also may be useful for monitoring antimicrobial resistance among healthcare-associated infections in hospitalized patients. The aim of this study was to characterize and describe the phenotypic and genotypic antimicrobial resistance of Escherichia coli and Klebsiella sp. strains from wastewater and from clinical isolates in a tertiary care children’s hospital in Lima, Perú.

Methods

We systematically collected 70 isolates of Escherichia coli and Klebsiella sp. from wastewater and 24 isolates of the same enterobacteria from blood and urine cultures at Instituto Nacional de Salud del Niño San Borja (INSN-SB) in Lima from December 2018 to May 2019. Susceptibility profiles were evaluated following CLSI criteria. We used the Jarlier method for the detection of extended-spectrum beta-lactamases (ESBL). For detection of AmpC beta-lactamases, we used discs of cefoxitin, ceftazidime, and ceftriaxone combined with cloxacillin and cefotaxime. For the detection of carbapenemase production, we used EDTA and phenylboronic acid inhibitors between meropenem and imipenem disks. We performed genomic sequencing for the detection of resistance genes and to perform a phylogenetic cluster analysis.

Results

We collected a total of 94 isolates (70 from wastewater and 24 from clinical samples). Among the total isolates, 19 (20.2%) were ESBL producers. The frequency of ESBL producers in wastewater was 7.1% (5/24), whereas the frequency of ESBL producers in clinical samples was 58.3% (14/70). The most frequent resistance genes were tet (variant 34 and A) and blaTEM-1. The frequency of tet(34) and tet(A) were 10% and 7%, respectively, in isolates from wastewater, whereas the frequency of these genes were 0% and 6%, respectively, in clinical isolates. The gene blaCTX-M-15 was present in isolates from wastewater (1%) and clinical samples (2%). Phylogenetic cluster analysis found no similarities between isolates from wastewater and to those from clinical samples, suggesting that the population of these enterobacteria were different in wastewater compared with clinical samples.

Conclusions

Enterobacteria from hospital wastewater may not reflect the profile of infections caused by these microorganisms. However, they may reflect the microbiological microbiota among patients, their visits, and hospital healthcare personnel. Further studies that compare the phenotypic and genotypic characteristics among isolates from wastewater and the enteric microbiota from these individuals would be necessary to assess this hypothesis.
#61: Antibiotic Use for Community-Acquired Pneumonia Among Hospitalized Children in Japan
Authors: Tao-Kidoguchi Chiaki , Ogawa Eiki , Shoji Kensuke , Miyairi Isao
Published: March 2021

Background

Judicious use of antimicrobials is the cornerstone of action against antimicrobial resistance. Respiratory tract infections account for over 80% of pediatric antibiotic use in Japan. Antibiotics are generally used empirically for most hospitalized patients with pneumonia although it is becoming clearer that viral etiologies account for approximately 70% of these cases. Defining the characteristics of patients who are managed with a short course of antibiotics and subsequently do well, may lead to setting clinical criteria for early termination of antibiotics.

Methods

We performed a retrospective descriptive analysis. Medical charts of patients aged 3 months to 18 years, who were admitted with a diagnosis of pneumonia, bronchitis, bronchiolitis, or asthma to the Department of Interdisciplinary medicine at the National Center for Child Health and Development from March 2018 through February 2019 were reviewed. Those who had respiratory symptoms and were started on antibiotics within 48 hours of hospitalization were included. Those who had a focus of infection elsewhere or were immunocompromised were excluded.

Results

Of the 556 candidates, 80 patients met the criteria. The median age was 1.5 years which included 42.5% (34/80) with comorbidities. Underlying conditions included 9 with trisomy 21, and 8 with perinatal issues. Rapid antigen testing was performed and 7 patients with RSV, 5 patients with influenza, 1 patient with human metapneumovirus were identified. The average duration of antibiotic therapy was 7.2 days (range 2–14 days). There were no statistical differences in the characteristics of patients who received antibiotics for more or less than 5 days. The positivity of the rapid antigen test tended to be higher in those who received antibiotics for a shorter period (25% vs. 15%). There were no differences in the rate of readmission or complications between the two groups.

Conclusion

We were unable to identify a clear characteristic of patients who received short courses of antibiotics for pneumonia. The trend observed for those who had a point of care testing may suggest that the use of a multiplex PCR testing covering a greater number of pathogens would influence physician behavior in antibiotic use.
#37: Clinical Characterization of the Cases Relating to the Outbreak of Clostridioides difficile, in a Third-level Hospital in Mexico City: Diagnosis, Treatment, and Relay
Authors: Samuel Ortiz , Elena Martínez María , Ramírez A Morayta
Published: March 2021

Background

Clostridioides difficile is an important cause of healthcare-associated infections. The epidemiology of C. difficile infection (CDI) in children has changed over the past few decades. There is now a higher incidence in hospitalized children, and there has been an emergence of community-onset infection. Neonates and young infants have high rates of colonization but rarely have symptoms. The well-known risk factor for CDI in children age 2 years or older is antibiotic use. Inflammatory bowel disease and cancer are associated with increased incidence and severity of CDI. Vancomycin or fidaxomicin is recommended for an initial episode of CDI. In environments where access to Vancomycin or Fidaxomycin is limited, it is suggested to use metronidazole for an initial episode of nonsevere CDI only.

Methods

A series of cases were carried out, in a study period from March to May 2018, total cases 8; the age group, sex, basic diagnosis, clinical findings, diagnostic method, and outcome in hospitalized patients in the Pediatric division of the “CMN 20 de Noviembre, ISSSTE” were described, where there is a total of 377 Sensitive beds, and 53 beds in the pediatric area of which 30 are not sensitive.

Results

We analyzed 8 cases of diarrhea with identification of C. difficile, in a period of 3 months, where there was a total of 148 admissions to the division of Pediatrics (100%) and presented a prevalence of 0.05% of the total income. Of those 8 cases reported, 37.5% were women and 62.5% men; The age fluctuated between 6 months and 18 years. All children had associated comorbidities. The frequency and type of comorbidities were Cancer 87.5% (Leukemias and Solid Tumors) and Neurological 12.5% ​​(Arterial Malformation and Neurological Sequelae). The main symptom that occurred was mucous diarrhea in 100% of patients, abdominal pain in 25% and evacuation with blood in 12.5% ​​of cases. All had a history of prior treatment with 100% broad-spectrum antibiotics, in a period of less than one month. All were treated with metronidazole (100%) and all presented clinical improvement, without complications; Similarly, all were diagnosed by PCR for toxin B (100%). The attributable risk of presenting Clostridioides disease in patients with Leukemia is 0.11.

Conclusions

Patients with Leukemia were the most affected during the C. difficile outbreak, of which 11 out of 100 of these patients are at risk of presenting C. difficile disease. The most important thing in these cases is prevention. Therefore, specific prevention measures were implemented to reduce the possibility of future outbreaks, such as handwashing with chlorexidine, contact isolation, handwashing every time there is contact with the patient, use of gloves when performing procedures, insulation of bedding in plastic bags and training of health personnel.