bluuebunny/crossref_metadata_2025 huggingface dataset:
Frontiers in urethra regeneration: current state and future perspective
Authors: Vasyutin Igor , Butnaru Denis , Lyundup Alexey , Timashev Peter , Vinarov Andrey , Kuznetsov Sergey , Atala Anthony , Zhang Yuanyuan
Published: June 2020

Despite the positive achievements attained, the treatment of male urethral strictures and hypospadiases still remains a challenge, particularly in cases of severe urethral defects. Complications and the need for additional interventions in such cases are common. Also, shortage of autologous tissue for graft harvesting and significant morbidity in the location of harvesting present problems and often lead to staged treatment. Tissue engineering provides a promising alternative to the current sources of grafts for urethroplasty. Since the first experiments in urethral substitution with tissue engineered grafts, this topic in regenerative medicine has grown remarkably, as many different types of tissue-engineered grafts and approaches in graft design have been suggested and testedin vivo. However, there have been only a few clinical trials of tissue-engineered grafts in urethral substitution, involving hardly more than a hundred patients overall. This indicates that the topic is still in its inception, and the search for the best graft design is continuing. The current review focuses on the state of the art in urethral regeneration with tissue engineering technology. It gives a comprehensive overview of the components of the tissue-engineered graft and an overview of the steps in graft development. Different cell sources, types of scaffolds, assembling approaches, options for vascularization enhancement and preclinical models are considered.
Digital environment, information systems and robotics: an absolute benefit or a new economic and political threat?
Authors: Botasheva A K , Anufrienko S V , Andish I B , Yefimova O V , Dyakonova M A
Published: June 2020

The introduction of new technologies into all spheres of human activity is rightly perceived by the scientific community as a qualitative leap in the development of human civilization. The effect of the introduction of information achievements, breakthrough technologies and communications, the spread of electronic data exchange, digitalization of the environment, etc. contributes not only to the growth of interdependence of the world economy, but also to the rapid improvement of the life quality. Therefore, the accepted set of values defines the central role of new technologies, which are often considered an absolute good. But the authors wonder whether this is an absolute good, or whether behind the facade of the actively developing process of exploiting the world and expanding science and technology into all types of human activity there is a fundamental change in the means of production and ways of human exploitation. The authors also conclude that the digitalization of the urban environment, appearance of autopilots and navigation systems, development of modern IT and nano-technologies, improvement of communication and production technologies open the questions not only of a military, but of an economic and political nature as well. The pursuit of technological efficiency does not take into account the “human dimension”, and the humanistic and sociocultural meaning of many technological achievements gets lost.
Synthesis of nanofibers organosiloxane structures under hydrothermal conditions
Authors: Cherkashina N I , Pavlenko Z V , Samoilova E S , Novosadov N I
Published: June 2020

The paper presents the possibility of producing polyhedral oligomeric silsesquioxanes (POSS) under hydrothermal conditions in a high-pressure reactor. POSS was prepared by hydrolytic polycondensation of cyclohexyl trichlorosilane under conditions of elevated temperature and pressure. Morphology and structure of the final products were characterized by X-ray diffraction (XRD), thermal analysis (TGA and DTA) in an atmosphere of argon, Fourier transform infrared spectrum (FT-IR) and scanning electron micrograph (SEM). The resulting compound is a nanofibers of a polyhedral oligomeric silsesquioxane. The diameter of the obtained nanofibers is 50 … 150 nm, and the length is from 200 nm to 30 μm.
Stocks of organic substance in post-agrogenic lands in Leningrad region
Authors: Danilov D A , Navalikhin S V , Vayman A A
Published: June 2020

We have analysed factors affecting the formation of organic matter stocks in sod-podzolic soils and post-agrogenic lands in the south-western part of the Leningrad region. There are many factors influencing the process of humus formation, which does not allow to reliably simulate the process of transformation of organic residues and the accumulation of humus in areas previously used for agricultural production. There is a connection in the differences in the specific density of the soil and the unequal content of humus in the genetic horizons of fallow soil compared to the arable layer of the field, where these horizons are mixed into a homogeneous mass. The data obtained show a high correlation between the humus content in the former arable horizon of soil with a clay fraction and pHKCI. At different successional stages of accumulation of organic matter in post-agrogenic lands is not the same, as the formation of different species composition of vegetation makes adjustments to this process. When determining humus stock in post-agrogenic lands, an error can reach to 30%. The main reason is the differences in the specific density of the soil and the unequal content of humus in the genetic horizons of fallow soil compared to the arable layer of the field, where these horizons are mixed into a homogeneous mass. The conclusion was made about different methods of soil sampling from arable lands and from post-agrogenic lands.
Comparative evaluation of air-water mixers operating with flotation plants
Authors: Grishin B M , Bikunova M V , Shein A I , Laskov NN , Sokolov I I
Published: June 2020

The article deals with theoretical and experimental studies of oily industrial wastewater flotation treatment using a saturator and vortex mixing devices (VMD) for preparing a water-air mixture. The use of VMD allows, in comparison with the saturator, to improve the efficiency of oil product removal on the flotator by 5-7% due to the greater gas saturation of the flotation volume. The energy consumption for preparing the water-air mixture in vortex mixers was on 8–10% lower than in flotation plants using a saturator.
Climate control in road-building machinery
Authors: Iovleva E L , Stepanov P A
Published: June 2020

Climate control is an advanced air conditioning system that allows controlling the temperature in the machinery cabin more effectively in any weather conditions. Today, almost all new road-building machinery is equipped with this system. This system allows adapting the temperature in the cabin according to your needs more effectively. Climate control allows controlling the climate in the cabin regardless of the weather conditions outside the machine. Climate control works just like home air conditioners, thanks to the automatic control of the heating, ventilation and air conditioning systems. With the help of electronics, the temperature is automatically maintained at the level set by the driver. This system is necessary not only to maintain a stable temperature in the cab, but also to maintain the efficiency and concentration of the driver. However, there is no air conditioning system in the old road construction machines. In the Republic of Sakha (Yakutia) the material and technological foundations in many road enterprises are outdated for now. And in order to keep the driver operating and protect his health, this article discusses the possibility to equip road-building machinery with climate control. THE Volvo BL61B forklift was chosen as an example. This machine initially lacked a climate control system, but thanks to a temperature control device, it was possible to achieve the optimum temperature in the cabin.
Improving the Fire-fighting Design of Silencers
Authors: Plitsyna O V , Rogova T N
Published: June 2020

This paper presents fire-fighting design of silencer formed by stepped partitions. Providing the distance between the partitions not exceeding a quarter of the wavelengths and forming the set of ducts with alternating expansions and narrowings create the possibilities for noise reduction and spark arresting. Slit silencer model testing on the stand contained doubled reverberant chambers with removable elements and diaphragm as well as on the stand with internal combustion chamber demonstrates the following: noise reduction is not less than 7.5 dB in a wide frequency range; pressure losses are not more than 120 Pa; sparks don’t pass. Correcting the silencer geometry allows forming the devices which acoustic and aerodynamic characteristics are similar to the characteristics of standard plate silencers. Calculating data show the dimensions of single and double silencer, ensuring spark arresting and requirement noise reduction in a gas flue.
GIS approaches to creating maps based on vegetation indices for forest management
Authors: Savchenko Y Y , Goleva O G , Korchagina I A , Lobanova Y S , Borzhikov T S
Published: June 2020

The article considers the main approaches to providing information support for improving forest management on the territory, taking into account the most up-to-date experience, modern approaches and implementing sustainable forestry management based on the data of remote sensing and geoinformational modelling. To identify the state of vegetation in the area under analysis, the authors of the article propose to introduce the definition of a normalized differential vegetation index. A characteristic feature of vegetation and its state is spectral reflectivity, which is characterized by substantial differences in reflecting radiation from different wavelengths. To obtain the necessary MODIS packages, we used the LAADS DAAC service supported by NASA. The data of this service are freely accessible, convenient for the user, and they are taken from a large number of satellites and their spectra. The optimal option for solving the tasks of compiling NDVI maps is using the geographic information system QGIS. Among the main advantages of this GIS we can consider user-friendliness and its multi-platform basis. For proper visualization of the NDVI map, a special discrete scale of values is used, the purpose of which is to differentiate between organic and non-organic nature, as well as determine the density of vegetation. The introduction of the proposed technology will significantly increase the mobility and effectiveness of forest management.
Ecological state of surface waters of rivers in industrial cities
Authors: Senotrusova S V , Svinukhov V G , Zhoglitcheva V V , Kurgaeva O L
Published: June 2020

The paper analyzes the chemical composition of the surface waters of a river flowing through an industrial city. Samples were taken in the Ussuri River, flowing through the city of Lesozavodsk. Four factors were derived that describe 78% of the variance of the variables. The first factor is associated with elements such as oxygen, BOD5 (Biological Oxygen Demand in 5 days), NH4, Fe, as well as phenols. Oil products and SSAS (Synthetic Surface-Active Substance) stood out in the second factor. The third factor is related to COD (Chemical Oxygen Demand), and NO3. Suspension and copper stood out as the fourth factor.
Import substitution as encouragement method of industrial production of Volgograd region
Authors: Shor Inna M , Shor Dmitriy M , Shelestova Dildarahon A , Batmanova Victoria V , Galamyan Lyubov I
Published: June 2020

The import substitution development which contributes to the encouragement of national industrial production under foreign sanctions is capable of providing the sustainability of enterprises in Russian regions. Herewith the measures which are taken today for the import substitution encouragement do not allow fully displaying the potential of its stimulating constituent. The goal of the research is the development of measures for import substitution growth as a method of import production in Volgograd region. The system approach, statistical analysis and dialectical method were used during the research. Volgograd region was taken as the example and the modern situation in import subsitution was analyzed. The SWOT analysis of industrial enterprises was conducted what allowed presenting the measures aimed at import subsitution growth as a method of encouragement of regional industrial enterprises. The authors made the conclusion about the necessity of an optimal combination of import substitution and export orientation which was based on the creation and development of enterprises which are focused on the world practice and which are profitable in global competition. This allows eliminating a number of drawbacks of import substitution which deal with the problem of a limited volume of the domestic market, construction of new industrial facilities, optimization of production processes, reduction of the monopolism, illegal economy and corruption.
Human gait modeling method
Authors: Sivolobov S V , Khoperskov A V , Bumagin V V
Published: June 2020

The article deals with problem of human gait modelling. Human gait analysis is used for various human identification tasks and for various purposes in medicine. Lagrange equations of the second kind in many research are used to model gait. We use a model of an anthropomorphic mechanism of five links to describe human movements. The mathematical model is implemented in the form of software that uses input data on the kinematics of a real gait. An important result of the study is the creation of an algorithm for calculating model parameters that best reproduce the gait of a particular person. Our approach is based on the application of a genetic algorithm to minimize a new special objective function, which depends on discrete generalized coordinates that depend on time. The dynamic picture significantly improves the quality of the model, which is able to reproduce the subtle features of the human gait.
Development of automation and virtualization instruments for the housing and utility services system
Authors: Toporov Dmitry Andreevich
Published: June 2020

The rationale of the research topic is determined by the importance of public administration instruments for the housing and utility services sector in the country. In this article, we considered theoretical and practical aspects of modern electronic technology used to improve the public administration of H&U and the principal trends in their development. We analyzed the “Smart H&U” system: its content, targets, value, advantages, along with the current practice of implementing this project and its results. We detailed the concept of the state information system for H&U (SIS H&U) and studied the legal foundations of the creation and operation of SIS H&U. We analyzed the importance of the state information system for ensuring the openness, accessibility and transparency of activities in the housing and utility services sector. The author listed the prospects and advantages of this system.
Intelligent decision support for information protection system’s design
Authors: Vitenburg E A , Nikishova A V , Umnitsyn M Yu , Omelchenko T A
Published: June 2020

The article defines the need to protect enterprise information systems. To ensure the security of enterprise information system, depending on the stage of a life cycle, it is necessary to design, control and upgrade the information protection system. We propose the approach to designing enterprise information system’s protection based on the method of intelligent decision support, which uses a neural network. To do so we form the mathematical model of intelligent decision support for designing of enterprise information system’s protection. It takes into account the data of monitoring and analysis of security events.
Optimizing cargo delivery employing vehicles of different carrying capacity
Authors: Volchkov V M , Korolyash V A , Rayushkin E S , Soloveva O U , Shvedov E G
Published: June 2020

Consider the problem of mathematical modeling. Making optimal use of vehicles of different carrying capacity can help minimize delivery costs. This article presents the models for finding the optimal delivery solution for ring roads and pendulum routes. The models were created for several car parks (depot) with vehicles of various carrying capacity. We also have taken into consideration that some routes are unavailable for particular types of transport.
Research and Engineering at Academic Institutions as LPP Factor: Russia Case Study
Authors: Yudina N V , Seliverstova O A
Published: June 2020

Language policy and planning (LPP) is an increasingly broad field today dealing with a number of complicated issues of utmost importance for the sustainable development of society in general and local communities in particular. In this view, it is necessary to create an efficient network and structure of actors all working towards the same goals. The paper seeks to explore the role of academic institutions as LPP actors with a focus on international cooperation in research and engineering as a major factor that impacts academic LPP at micro-level and shapes foreign language acquisition agenda at the macro-level. The paper presents a case study focused on Russian LPP and considers its current concerns and solutions.
Accessibility of urban and rural environment of the Kola North of Russia (Murmansk region) for disabled people
Authors: Zhigunova G V , Afonkina Yu A
Published: June 2020

In today’s Russian society, people with disabilities cannot successfully join society because of the existing social barriers in various spheres of activity. As a result, they have limited access to social resources and a higher social status. In this regard, ensuring the independent life of disabled people is an urgent task for Russian society. The present research aims at identifying the level of accessibility of the social environment in the North of Russia for people with disabilities. Research methods are represented with general scientific methods of cognition, analysis of scientific literature, regulatory documents, data of secondary sociological research, and results of the method of observation conducted by the authors in 2018-2019. The analysis showed that today there are social barriers in all spheres of activity, and the level of infrastructure’s accessibility in rural settlements is much worse than in urban environment. The obtained results can be used in urban planning and social practice with the aim to transform the social environment and ensure its accessibility for people with disabilities.
Steam oxidation behavior of Y-bearing cladding tube with aluminizing coating
Authors: Zhang Xiaoxin , Hong Zhiyuan , Yang Jiabao , Chen Yingxue , Zeng Xian , Yan Qingzhi
Published: June 2020

A kind of Y-bearing ferritic/martensitic fuel cladding tube with qualified dimensions, acceptable mechanical properties as well as good flattening and flaring performance was manufactured recently by our group. In this paper, to improve and further evaluate its oxidation resistance, the cladding tube was aluminized firstly and then subjected to high temperature steam oxidation at 1200 °C for 8 h. The results indicated that aluminizing coating with gradient content of Al was prepared on the tube successfully. And the matrix microstructure was transformed from tempered martensite into ferrite during aluminizing. Weight gains after high temperature steam oxidation were 72.7 and 1.48 mg cm−2 for the bare and aluminized tubes, respectively. The latter one exhibited better oxidation resistance due to the generated dense aluminum oxide film. Meanwhile, Kirkendall pores were formed near oxidation surface and should be eliminated for the real application of the aluminized tube in the future.
Jump or kink: on super-efficiency in segmented linear regression breakpoint estimation
Authors: Chen Yining
Published: June 2020

We consider the problem of segmented linear regression with a single breakpoint, with the focus on estimating the location of the breakpoint. If $n$ is the sample size, we show that the global minimax convergence rate for this problem in terms of the mean absolute error is $O(n^{-1/3})$. On the other hand, we demonstrate the construction of a super-efficient estimator that achieves the pointwise convergence rate of either $O(n^{-1})$ or $O(n^{-1/2})$ for every fixed parameter value, depending on whether the structural change is a jump or a kink. The implications of this example and a potential remedy are discussed.
The Need for Culturally Competent Care Within Gastroenterology Services: Evidence from Research with Adults of South Asian Origin Living with Inflammatory Bowel Disease
Authors: Mukherjee Suzanne , Beresford Bryony , Atkin Karl , Sebastian Shaji
Published: June 2020

Background and Aims

It is widely acknowledged that the incidence of inflammatory bowel disease [IBD] is rising within South Asian populations, yet research into the experiences of this group of patients is rare. In this study the lived experiences of UK South Asian adults with IBD, including support from gastroenterology services, was investigated.

Methods

A sample of 33 patients representing the diversity of the UK South Asian population were recruited through five gastroenterology clinics in England. In-depth semi-structured interviews were conducted, audio-recorded, transcribed and analysed using the Framework approach.

Results

Although many experiences align with those of the general IBD population, participants believed that South Asian cultures and/or religions can lead to additional challenges. These are linked to: family and friends’ understanding of IBD; self and family attributions regarding IBD; stigma surrounding ill health; the taboo of bowel symptoms; managing ‘spicy food’; beliefs about food and ill health; roles within the family; living with extended family; the use of complementary and alternative therapies; and visits to family overseas. Religious faith helped many to cope with having IBD, but symptoms could hamper their ability to practise faith. Gastroenterology services were viewed positively, but unmet needs were identified, some of which were culturally specific.

Conclusion

Gastroenterology services have an important role to play in helping patients to overcome the challenges they encounter in their everyday life, both by providing individual patients with culturally appropriate care and advice, and via interventions to increase awareness and understanding of IBD within wider South Asian communities.
Prokaryotic names: the bold and the beautiful
Authors: Oren Aharon
Published: June 2020

In recent years, names of ∼170 new genera and ∼1020 new species were added annually to the list of prokaryotic names with standing in the nomenclature. These names were formed in accordance with the Rules of the International Code of Nomenclature of Prokaryotes. Most of these names are not very interesting as specific epithets and word elements from existing names are repeatedly recycled. The rules of the Code provide many opportunities to create names in far more original ways. A survey of the lists of names of genera and species of prokaryotes shows that there is no lack of interesting names. The annotated selection presented here proves that at least some authors have exploited the possibilities allowed by the rules of the Code to name novel organisms in ways that are more attractive. I here call upon all colleagues who describe new taxa to devote more thought to the naming of new genera and species. It takes some effort, and it requires proper use of the lexicon of Classical Greek and Latin as well as an understanding of the Code and the guidelines of its orthography appendix. Creation of attractive names will boost the general interest in prokaryotic nomenclature.
A Comprehensive Multi-Omic Approach Reveals a Relatively Simple Venom in a Diet Generalist, the Northern Short-Tailed Shrew, Blarina brevicauda
Authors: Hanf Zachery R , Chavez Andreas S
Published: June 2020

Animals that use venom to feed on a wide diversity of prey may evolve a complex mixture of toxins to target a variety of physiological processes and prey-defense mechanisms. Blarina brevicauda, the northern short-tailed shrew, is one of few venomous mammals, and is also known to eat evolutionarily divergent prey. Despite their complex diet, earlier proteomic and transcriptomic studies of this shrew’s venom have only identified two venom proteins. Here, we investigated with comprehensive molecular approaches whether B. brevicauda venom is more complex than previously understood. We generated de novo assemblies of a B. brevicauda genome and submaxillary-gland transcriptome, as well as sequenced the salivary proteome. Our findings show that B. brevicauda’s venom composition is simple relative to their broad diet and is likely limited to seven proteins from six gene families. Additionally, we explored expression levels and rate of evolution of these venom genes and the origins of key duplications that led to toxin neofunctionalization. We also found three proteins that may be involved in endogenous self-defense. The possible synergism of the toxins suggests that vertebrate prey may be the main target of the venom. Further functional assays for all venom proteins on both vertebrate and invertebrate prey would provide further insight into the ecological relevance of venom in this species.
Machine Learning in Aging: An Example of Developing Prediction Models for Serious Fall Injury in Older Adults
Authors: Speiser Jaime Lynn , Callahan Kathryn E , Houston Denise K , Fanning Jason , Gill Thomas M , Guralnik Jack M , Newman Anne B , Pahor Marco , Rejeski W Jack , Miller Michael E
Published: June 2020

Background

Advances in computational algorithms and the availability of large datasets with clinically relevant characteristics provide an opportunity to develop machine learning prediction models to aid in diagnosis, prognosis, and treatment of older adults. Some studies have employed machine learning methods for prediction modeling, but skepticism of these methods remains due to lack of reproducibility and difficulty in understanding the complex algorithms that underlie models. We aim to provide an overview of two common machine learning methods: decision tree and random forest. We focus on these methods because they provide a high degree of interpretability.

Method

We discuss the underlying algorithms of decision tree and random forest methods and present a tutorial for developing prediction models for serious fall injury using data from the Lifestyle Interventions and Independence for Elders (LIFE) study.

Results

Decision tree is a machine learning method that produces a model resembling a flow chart. Random forest consists of a collection of many decision trees whose results are aggregated. In the tutorial example, we discuss evaluation metrics and interpretation for these models. Illustrated using data from the LIFE study, prediction models for serious fall injury were moderate at best (area under the receiver operating curve of 0.54 for decision tree and 0.66 for random forest).

Conclusions

Machine learning methods offer an alternative to traditional approaches for modeling outcomes in aging, but their use should be justified and output should be carefully described. Models should be assessed by clinical experts to ensure compatibility with clinical practice.
Effect of rare coding variants in the CFI gene on Factor I expression levels
Authors: de Jong Sarah , Volokhina Elena B , de Breuk Anita , Nilsson Sara C , de Jong Eiko K , van der Kar Nicole C A J , Bakker Bjorn , Hoyng Carel B , van den Heuvel Lambert P , Blom Anna M , den Hollander Anneke I
Published: June 2020

Factor I (FI) is one of the main inhibitors of complement activity, and numerous rare coding variants have been reported in patients with age-related macular degeneration, atypical hemolytic uremic syndrome and C3 glomerulopathy. Since many of these variants are of unknown clinical significance, this study aimed to determine the effect of rare coding variants in the complement factor I (CFI) gene on FI expression. We measured FI levels in plasma samples of carriers of rare coding variants and in vitro in the supernatants of epithelial cells expressing recombinant FI. FI levels were measured in 177 plasma samples of 155 individuals, carrying 24 different rare coding variants in CFI. In carriers of the variants p.Gly119Arg, p.Leu131Arg, p.Gly188Ala and c.772G>A (r.685_773del), significantly reduced FI plasma levels were detected. Furthermore, recombinant FI expression levels were determined for 126 rare coding variants. Of these variants 68 (54%) resulted in significantly reduced FI expression in supernatant compared to wildtype (WT). The recombinant protein expression levels correlated significantly with the FI level in plasma of carriers of CFI variants. In this study, we performed the most comprehensive FI expression level analysis of rare coding variants in CFI to date. More than half of CFI variants lead to reduced FI expression, which might impair complement regulation in vivo. Our study will aid the interpretation of rare coding CFI variants identified in clinical practice, which is in particular important in light of patient inclusion in ongoing clinical trials for CFI gene supplementation in AMD.
Grand Challenges in Comparative Tooth Biology
Authors: Hulsey C Darrin , Cohen Karly E , Johanson Zerina , Karagic Nidal , Meyer Axel , Miller Craig T , Sadier Alexa , Summers Adam P , Fraser Gareth J
Published: June 2020

Teeth are a model system for integrating developmental genomics, functional morphology, and evolution. We are at the cusp of being able to address many open issues in comparative tooth biology and we outline several of these newly tractable and exciting research directions. Like never before, technological advances and methodological approaches are allowing us to investigate the developmental machinery of vertebrates and discover both conserved and excitingly novel mechanisms of diversification. Additionally, studies of the great diversity of soft tissues, replacement teeth, and non-trophic functions of teeth are providing new insights into dental diversity. Finally, we highlight several emerging model groups of organisms that are at the forefront of increasing our appreciation of the mechanisms underlying tooth diversification.
Reproduction Within a Hierarchical Society from a Female’s Perspective
Authors: Holekamp Kay E , Strauss Eli D
Published: June 2020

The reproductive biology of many female mammals is affected by their social environment and their interactions with conspecifics. In mammalian societies structured by linear dominance hierarchies, such as that of the spotted hyena (Crocuta crocuta), a female’s social rank can have profound effects on both her reproductive success and her longevity. In this species, social rank determines priority of access to food, which is the resource limiting reproduction. Due largely to rank-related variation in access to food, reproduction from the perspective of a female spotted hyena can only be understood in the context of her position in the social hierarchy. In this review, we examine the effects of rank on the various phases of reproduction, from mating to weaning. Summed over many individual reproductive lifespans, the effect of rank at these different reproductive phases leads to dramatic rank-related variation in fitness among females and their lineages. Finally, we ask why females reproduce socially despite these apparent costs of group living to low-ranking females. Gregariousness enhances the fitness of females regardless of their positions in the social hierarchy, and females attempting to survive and reproduce without clanmates lose all their offspring. The positive effects of gregariousness appear to result from having female allies, both kin and non-kin, who cooperate to advertise and defend a shared territory, acquire, and defend food resources, maintain the status quo, and occasionally also to rise in social rank.
Real-time TDM-based optimization of continuous-infusion meropenem for improving treatment outcome of febrile neutropenia in oncohaematological patients: results from a prospective, monocentric, interventional study
Authors: Cojutti Pier Giorgio , Lazzarotto Davide , Candoni Anna , Dubbini Maria Vittoria , Zannier Maria Elena , Fanin Renato , Pea Federico
Published: June 2020

Objectives

To assess the role that real-time therapeutic drug monitoring (TDM)-guided optimization of continuous-infusion (CI) meropenem may have in maximizing empirical treatment and in preventing breakthrough infection and/or colonization with carbapenem-resistant Enterobacteriaceae (CRE) among oncohaematological patients with febrile neutropenia (FN).

Methods

A monocentric, interventional, prospective study was conducted. The pharmacodynamic (PD) target was a steady-state meropenem concentration-to-MIC ratio (Css/MIC) of 4–8. The primary endpoint was 14 day all-cause mortality. The secondary endpoint was the prevalence of CRE colonization in rectal swabs of patients rehospitalized within 3 months.

Results

Among the 75 patients enrolled, most (56%) had AML, almost half (37/75, 49.3%) underwent HSCT and one-third (32%) received meropenem as monotherapy. Meropenem dosages were adjusted in 30.1% of TDM reassessments. Gram-negative infections were microbiologically documented in 20.0% of patients. All of the 12 patients having infections caused by in vitro meropenem-susceptible pathogens attained the desired PD target and were cured. Three patients had infections caused by in vitro meropenem-resistant pathogens. Two of these achieved a Css/MIC target of 1 and were cured; the other one achieved a suboptimal PD target (0.59) and died. The 14 day all-cause mortality (10.7%) was significantly associated, at multivariate regression, with HSCT (OR 0.086, 95% CI 0.008–0.936, P = 0.044) and with augmented renal clearance (OR 10.846, 95% CI 1.534–76.672, P = 0.017). None of the patients who had hospital readmissions in the 3 month follow-up (63/75) had CRE colonization in rectal swabs.

Conclusions

Real-time TDM-guided CI meropenem may be a useful approach for attaining adequate exposure and preventing CRE emergence in FN oncohaematological patients.
Genomic prediction using pooled data in a single-step genomic best linear unbiased prediction framework
Authors: Baller Johnna L , Kachman Stephen D , Kuehn Larry A , Spangler Matthew L
Published: June 2020

Economically relevant traits are routinely collected within the commercial segments of the beef industry but are rarely included in genetic evaluations because of unknown pedigrees. Individual relationships could be resurrected with genomics, but this would be costly; therefore, pooling DNA and phenotypic data provide a cost-effective solution. Pedigree, phenotypic, and genomic data were simulated for a beef cattle population consisting of 15 generations. Genotypes mimicked a 50k marker panel (841 quantitative trait loci were located across the genome, approximately once per 3 Mb) and the phenotype was moderately heritable. Individuals from generation 15 were included in pools (observed genotype and phenotype were mean values of a group). Estimated breeding values (EBV) were generated from a single-step genomic best linear unbiased prediction model. The effects of pooling strategy (random and minimizing or uniformly maximizing phenotypic variation within pools), pool size (1, 2, 10, 20, 50, 100, or no data from generation 15), and generational gaps of genotyping on EBV accuracy (correlation of EBV with true breeding values) were quantified. Greatest EBV accuracies of sires and dams were observed when there was no gap between genotyped parents and pooled offspring. The EBV accuracies resulting from pools were usually greater than no data from generation 15 regardless of sire or dam genotyping. Minimizing phenotypic variation increased EBV accuracy by 8% and 9% over random pooling and uniformly maximizing phenotypic variation, respectively. A pool size of 2 was the only scenario that did not significantly decrease EBV accuracy compared with individual data when pools were formed randomly or by uniformly maximizing phenotypic variation (P > 0.05). Pool sizes of 2, 10, 20, or 50 did not generally lead to statistical differences in EBV accuracy than individual data when pools were constructed to minimize phenotypic variation (P > 0.05). Largest numerical increases in EBV accuracy resulting from pooling compared with no data from generation 15 were seen with sires with prior low EBV accuracy (those born in generation 14). Pooling of any size led to larger EBV accuracies of the pools than individual data when minimizing phenotypic variation. Resulting EBV for the pools could be used to inform management decisions of those pools. Pooled genotyping to garner commercial-level phenotypes for genetic evaluations seems plausible although differences exist depending on pool size and pool formation strategy.
Effects of supplemental xylanase on health of the small intestine in nursery pigs fed diets with corn distillers’ dried grains with solubles
Authors: Chen Hongyu , Zhang Shihai , Kim Sung Woo
Published: June 2020

Forty pigs [10.7 ± 1.2 kg initial body weight (BW) at 6 wk of age] were used in a 21-d study to evaluate the effects of supplemental xylanase (Hostazym X 100, Huvepharma, Inc., Peachtree City, GA) in nursery diets on digesta viscosity, nutrient digestibility, health of the small intestine, and growth performance when supplemented with corn distillers’ dried grains with solubles (DDGS). Pigs were individually housed and randomly allotted to four treatments in a 2 × 2 factorial arrangement (n = 20/factor, 0% or 30% DDGS and 0 or 1,500 endo-pentosanase unit/kg xylanase as two factors) based on sex and initial BW. Feed intake and BW were recorded weekly. On day 15 of the study, TiO2 in diets (0.3%) was used as an indigestible marker to calculate apparent ileal digestibility (AID). Plasma samples were collected on day 19 to measure tumor necrosis factor-alpha (TNF-α), malondialdehyde, and peptide YY. On day 21, all pigs were euthanized to collect tissues from duodenum, jejunum, and colon to measure morphology, TNF-α, and malondialdehyde concentrations. Distal jejunal digesta were collected to measure viscosity. Ileum digesta were collected to measure AID of nutrients. During the entire period, supplemental xylanase increased (P < 0.05) average daily gain (ADG; 616 to 660 g/d) of nursery pigs, whereas DDGS (0 or 30%) did not affect ADG. On week 3, average daily feed intake (ADFI) was increased (P < 0.05) when fed DDGS (1,141 to 1,267 g/d) and there was an interaction (P < 0.05) between two factors indicating that supplemental xylanase decreased ADFI when DDGS was used in a diet. Use of DDGS increased (P < 0.05) viscosity [1.86 to 2.38 centipoise (cP)], whereas supplemental xylanase reduced (P < 0.05) viscosity (2.27 to 1.96 cP) of jejunal digesta. The AID of dry matter (DM) and gross energy (GE) were improved (P < 0.05) by supplemental xylanase. Plasma TNF-α was decreased (P < 0.05, 108.5 to 69.9 pg/mL) by supplemental xylanase. Use of DDGS reduced (P < 0.05) villus height:crypt depth ratio (1.46 to 1.27), whereas supplemental xylanase increased (P < 0.05) the crypt depth (360 to 404 µm) in duodenum. In conclusion, feeding a diet with 30% DDGS to nursery pigs for 3 wk had no negative effect on growth performance, whereas reduced AID of DM and GE, increased TNF-α level in colon tissue, and reduced the ratio of villus height to crypt depth. Dietary supplementation of xylanase reduced digesta viscosity improving AID of nutrients, reduced inflammatory response, and altered intestinal morphology, collectively improving ADG of nursery pigs regardless of the use of DDGS in a diet.
The Novel Psychoactive Substance Cumyl-CH-MEGACLONE: Human Phase-I Metabolism, Basic Pharmacological Characterization and Comparison to Other Synthetic Cannabinoid Receptor Agonists with a γ-Carboline-1-One Core
Authors: Haschimi Belal , Giorgetti Arianna , Mogler Lukas , Nagy Tibor Zsigmond , Kramer Selina , Halter Sebastian , Boros Sándor , Dobos Adrienn , Hidvégi Előd , Auwärter Volker
Published: June 2020

Synthetic cannabinoids (SC) remain one of the largest groups of new psychoactive substances on the European drug market. In December 2018, Cumyl-CH-MEGACLONE, a novel SC based on a γ-carboline-1-one core structure, was firstly identified in Hungary and later also other European countries. This work aims to reveal the pharmacological characteristics and phase-I metabolism of Cumyl-CH-MEGACLONE and compare the data to its analogs Cumyl-PEGACLONE and 5F-Cumyl-PEGACLONE. The purified substance was characterized by means of gas chromatography–mass spectrometry (GC–MS), liquid chromatography–quadrupole time-of-flight mass spectrometry (LC–QToF-MS), attenuated total reflection infrared spectroscopy (ATR-FTIR) and nuclear magnetic resonance spectroscopy. Phase-I metabolites were identified by LC–QToF-MS analysis combined with a scheduled precursor ion list of authentic urine samples and confirmed by comparison with metabolites built in vitro by pooled human liver microsome assays. Pharmacological data were obtained in a competitive ligand binding assay and a receptor activation assay at the human cannabinoid receptor 1 (hCB1). The structure of 5-cyclohexylmethyl-2-(2-phenylpropan-2-yl)-2,5-dihydro-1H-pyrido[4,3-b]indol-1-one (semisystematic name: Cumyl-CH-MEGACLONE) was identified in a herbal blend as the main active ingredient. Investigation of phase-I biotransformation of Cumyl-CH-MEGACLONE led to three monohydroxylated metabolites (M08, M10 and M13) as reliable urinary markers for proof of consumption. At the hCB1, Cumyl-CH-MEGACLONE shows high binding affinity with Ki = 1.01 nM (2.5-fold higher than JWH-018), an EC50 of 1.22 nM and high efficacy with EMAX = 143.4% above constitutive activity of the receptor (1.13-fold higher than JWH-018). Comparison to the analogs 5F-Cumyl-PEGACLONE and Cumyl-PEGACLONE (both are hCB1 full agonists carrying a 5-fluoropentyl or pentyl chain instead of the cyclohexylmethyl moiety) suggests that Cumyl-CH-MEGACLONE is more likely to resemble the pharmacologic profile of the latter one.
Report on a New Opioid NPS: Chemical and In Vitro Functional Characterization of a Structural Isomer of the MT-45 Derivative Diphenpipenol
Authors: Cannaert Annelies , Hulpia Fabian , Risseeuw Martijn , Van Uytfanghe Katleen , Deconinck Eric , Van Calenbergh Serge , Blanckaert Peter , Stove Christophe
Published: June 2020

In this paper, the identification and full characterization of a novel non-fentanyl opioid sourced online, which is a member of the 1-substituted-4-(1,2-diphenylethyl)piperazine derivatives related to MT-45, is reported. The sample was sold under the name “diphenpipenol,” (3-[2-[4-(2-methoxyphenyl)piperazin-1-yl]-2-phenylethyl]phenol), although extensive NMR analysis showed that the product obtained was actually a diphenpipenol structural isomer, (2-[4-(2-methoxyphenyl)piperazin-1-yl]-1,2-diphenylethanol). Liquid chromatography time-of-flight mass spectrometry identified an exact mass for the protonated molecule of m/z 389.2264, with two prominent fragment ions (m/z 91.0567 and 150.0937), which were not reported in earlier literature describing MT-45 derivatives. The chemical characterization was finalized by gas chromatography–mass spectrometry, high-performance liquid chromatography diode array detector and Fourier-transform infrared spectroscopy analyses. This product is a clear example of the trend that new non-fentanyl opioids are reappearing on the recreational drug market to escape the recent changes in (inter)national legislation concerning fentanyl analogues. Although in this particular case, the product’s potency and efficacy were relatively low, other new non-fentanyl opioids might possess stronger potencies and therefore pose greater health risks for ignorant users. The fact that the product was sold under the wrong name further demonstrates the well-known problematic issue of a mismatch between the adverted and true identity, confirming the irregularities of the online new psychoactive substances market.
Cannabis sativa as a Host of Rice Root Aphid (Hemiptera: Aphididae) in North America
Authors: Cranshaw Whitney , Wainwright-Evans Suzanne
Published: June 2020

Rice root aphid, Rhopalosiphum rufiabdominale (Sasaki), is a cosmopolitan species widespread in North America. Most records of this insect are of its association with roots of grasses and sedges, but known hosts also include numerous broadleaved plants both grown outdoors and in greenhouses. Indoor grown Cannabis sativa L., particularly when intensively grown for marijuana production, has also emerged as a common host for this insect in the United States and Canada. On this crop, it has an anholocyclic life cycle where it is almost entirely found in association with plant roots. Colonization of new plants is largely by alate forms that may emerge from soil in large numbers as plants near maturity.
Collection and Rearing of Container Mosquitoes and a 24-h Addition to the CDC Bottle Bioassay
Authors: Parker Casey
Published: June 2020

Container mosquitoes (Diptera: Culicidae) oviposit their eggs in both natural and artificial containers. Many container mosquito species also serve as important vectors of disease-causing pathogens including Aedes aegypti, Ae. albopictus, and Ae. triseriatus. Control of these species can be done through the use of adulticide sprays. The efficacy of these treatments is highly dependent on the insecticide susceptibility status of the local mosquito populations. This paper provides protocols on collecting and rearing container mosquitoes for use in the Centers for Disease Control and Prevention (CDC) bottle bioassay. A brief description of the CDC bottle bioassay is provided as well as a standardized protocol for the incorporation of a 24-h mortality to the CDC bottle bioassay. Results from this 24-h holding addition to the CDC bottle bioassay reveal that some forms of resistance may be missed without the incorporation of the additional mortality reading. These protocols provide a foundation for new laboratories to establish rearing protocols and begin conducting resistance monitoring.
Laboratory Assay Evaluation Demystified: A Review of Key Factors Influencing Interpretation of Test Results Using Different Assays for SARS-CoV-2 Infection Diagnosis
Authors: Pham Huy P , Staley Elizabeth M , Raju Dheeraj , Marin Maximo J , Kim Chong H
Published: June 2020

Laboratory tests are an integral part of the diagnosis and management of patients; however, these tests are far from perfect. Their imperfections can be due to patient health condition, specimen collection, and/or technological difficulty with performing the assay and/or interpretation. To be useful clinically, testing requires calculation of positive predictive values (PPVs) and negative predictive values (NPVs). During the current global pandemic of COVID-19 (coronavirus disease 2019), multiple assays with unknown clinical sensitivity and specificity have been rapidly developed to aid in the diagnosis of the disease. Due to a lack of surveillance testing, the prevalence of COVID-19 remains unknown. Hence, using this situation as an clinical example, the goal of this article is to clarify the key factors that influence the PPV and NPV yielded by diagnostic testing, By doing so, we hope to offer health-care providers information that will help them better understand the potential implications of utilizing these test results in clinical patient management.
Peptide–Oleate Complexes Create Novel Membrane-Bound Compartments
Authors: Hansen Jesper S , Tran Tuan Hiep , Cavalera Michele , Paul Sanchari , Chaudhuri Arunima , Lindkvist-Petersson Karin , Ho James C S , Svanborg Catharina
Published: June 2020

A challenging question in evolutionary theory is the origin of cell division and plausible molecular mechanisms involved. Here, we made the surprising observation that complexes formed by short alpha-helical peptides and oleic acid can create multiple membrane-enclosed spaces from a single lipid vesicle. The findings suggest that such complexes may contain the molecular information necessary to initiate and sustain this process. Based on these observations, we propose a new molecular model to understand protocell division.