bluuebunny/crossref_metadata_2025 huggingface dataset:
Nutritional perspectives on sickle cell disease in Africa: a systematic review
Authors: Nartey Eunice Berko , Spector Jonathan , Adu-Afarwuah Seth , Jones Catherine L. , Jackson Alan , Ohemeng Agartha , Shah Rajiv , Koryo-Dabrah Alice , Kuma Amma Benneh-Akwasi , Hyacinth Hyacinth I. , Steiner-Asiedu Matilda
Published: March 2021

Background

Sickle cell disease (SCD) is an inherited blood disorder that predominantly affects individuals in sub-Saharan Africa. However, research that elucidates links between SCD pathophysiology and nutritional status in African patients is lacking. This systematic review aimed to assess the landscape of studies in sub-Saharan Africa that focused on nutritional aspects of SCD, and highlights gaps in knowledge that could inform priority-setting for future research.

Methods

The study was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Inclusion criteria comprised original, peer-reviewed research published between January 1995 and November 2020 involving individuals in Africa with any phenotypic variant of SCD and at least one nutritional status outcome. Nutritional status outcomes were defined as those that assessed dietary intakes, growth/anthropometry, or nutritional biomarkers. Databases used were Ovid Embase, Medline, Biosis and Web of Science.

Results

The search returned 526 articles, of which 76 were included in the final analyses. Most investigations (67%) were conducted in Nigeria. Studies were categorized into one of three main categories: descriptive studies of anthropometric characteristics (49%), descriptive studies of macro- or micronutrient status (41%), and interventional studies (11%). Findings consistently included growth impairment, especially among children and adolescents from sub-Saharan Africa. Studies assessing macro- and micronutrients generally had small sample sizes and were exploratory in nature. Only four randomized trials were identified, which measured the impact of lime juice, long-chain fatty acids supplementation, ready-to-use supplementary food (RUSF), and oral arginine on health outcomes.

Conclusions

The findings reveal a moderate number of descriptive studies, most with small sample sizes, that focused on various aspects of nutrition and SCD in African patients. There was a stark dearth of interventional studies that could be used to inform evidence-based changes in clinical practice. Findings from the investigations were generally consistent with data from other regional settings, describing a significant risk of growth faltering and malnutrition among individuals with SCD. There is an unmet need for clinical research to better understand the potential benefits of nutrition-related interventions for patients with SCD in sub-Saharan Africa to promote optimal growth and improve health outcomes.
Automatic question generation and answer assessment: a survey
Authors: Das Bidyut , Majumder Mukta , Phadikar Santanu , Sekh Arif Ahmed
Published: March 2021

Learning through the internet becomes popular that facilitates learners to learn anything, anytime, anywhere from the web resources. Assessment is most important in any learning system. An assessment system can find the self-learning gaps of learners and improve the progress of learning. The manual question generation takes much time and labor. Therefore, automatic question generation from learning resources is the primary task of an automated assessment system. This paper presents a survey of automatic question generation and assessment strategies from textual and pictorial learning resources. The purpose of this survey is to summarize the state-of-the-art techniques for generating questions and evaluating their answers automatically.
Prognostic biomarkers in predicting mortality in respiratory patients with ventilator-associated pneumonia
Authors: Abdelaleem Nermeen A. , Makhlouf Hoda A. , Nagiub Eman M. , Bayoumi Hassan A.
Published: March 2021

Background

Ventilator-associated pneumonia (VAP) is the most common nosocomial infection. Red cell distribution width (RDW) and neutrophil-lymphocyte ratio (NLR) are prognostic factors to mortality in different diseases. The aim of this study is to evaluate prognostic efficiency RDW, NLR, and the Sequential Organ Failure Assessment (SOFA) score for mortality prediction in respiratory patients with VAP.

Results

One hundred thirty-six patients mechanically ventilated and developed VAP were included. Clinical characteristics and SOFA score on the day of admission and at diagnosis of VAP, RDW, and NLR were assessed and correlated to mortality. The average age of patients was 58.80 ± 10.53. These variables had a good diagnostic performance for mortality prediction AUC 0.811 for SOFA at diagnosis of VAP, 0.777 for RDW, 0.728 for NLR, and 0.840 for combined of NLR and RDW. The combination of the three parameters demonstrated excellent diagnostic performance (AUC 0.889). A positive correlation was found between SOFA at diagnosis of VAP and RDW (r = 0.446, P < 0.000) and with NLR (r = 0.220, P < 0.010).

Conclusions

NLR and RDW are non-specific inflammatory markers that could be calculated quickly and easily via routine hemogram examination. These markers have comparable prognostic accuracy to severity scores. Consequently, RDW and NLR are simple, yet promising markers for ICU physicians in monitoring the clinical course, assessment of organ dysfunction, and predicting mortality in mechanically ventilated patients. Therefore, this study recommends the use of blood biomarkers with the one of the simplest ICU score (SOFA score) in the rapid diagnosis of critical patients as a daily works in ICU.
De novo formation of early endosomes during Rab5-to-Rab7a transition
Authors: Skjeldal Frode Miltzow , Haugen Linda Hofstad , Mateus Duarte , Frei Dominik M. , Rødseth Anna Vik , Hu Xian , Bakke Oddmund
Published: March 2021

Rab5 and Rab7a are the main determinants of early and late endosomes and are important regulators of endosomal progression. The transport from early endosomes to late endosome seems to be regulated through an endosomal maturation switch, where Rab5 is gradually exchanged by Rab7a on the same endosome. Here, we provide new insight into the mechanism of endosomal maturation, for which we have discovered a stepwise Rab5 detachment, sequentially regulated by Rab7a. The initial detachment of Rab5 is Rab7a independent and demonstrates a diffusion-like first-phase exchange between the cytosol and the endosomal membrane, and a second phase, in which Rab5 converges into specific domains that detach as a Rab5 indigenous endosome. Consequently, we show that early endosomal maturation regulated through the Rab5-to-Rab7a switch induces the formation of new fully functional Rab5-positive early endosomes. Progression through stepwise early endosomal maturation regulates the direction of transport and, concomitantly, the homeostasis of early endosomes.
Maintaining Power Output with Accumulating Levels of Work Done Is a Key Determinant for Success in Professional Cycling
Authors: VAN ERP TEUN , SANDERS DAJO , LAMBERTS ROBERT P.
Published: March 2021

Introduction

This study aimed to investigate if performance measures are related to success in professional cycling and to highlight the influence of prior work done on these performance measures and success.

Methods

Power output data from 26 professional cyclists, in a total of 85 seasons, collected between 2012 and 2019, were analyzed. The cyclists were classified as “climber” or “sprinter” and into category 1 (CAT.1; ≥400 PCSpoints (successful)) and CAT.2 (<400 PCSpoints (less successful)), based on the number of procyclingstats-points (PCSpoints) collected for that particular season. Maximal mean power outputs (MMP) for 20 min, 5 min, 1 min, and 10 s relative to body weight for every season were determined. To investigate the influence of prior work done on these MMP values, six different levels of completed work done were determined, which are based on the amount of completed kilojoules per kilogram (0, 10, 20, 30, 40, and 50 kJ·kg−1). Subsequently, the decline in MMP for each duration (if any) after each level of completed work done was evaluated.

Results

Mixed model revealed that prior work done affects the performance of climbers and sprinters negatively. However, CAT.1 climbers have a smaller decline in 20- and 5-min MMP after high amounts of work done compared with CAT.2 climbers. Similarly, CAT.1 sprinters have a smaller decline in 10-s and 1-min MMP after high amounts of work done compared with CAT.2 sprinters.

Conclusions

It seems that the ability to maintain high MMP (corresponding with the specialization of a cyclist) after high amounts of work done (i.e., fatigue) is an important parameter for success in professional cyclists. These findings suggest that assessing changes in MMP after different workloads might be highly relevant in professional cycling.
РАЗРАБОТКА СИСТЕМЫ УЧЕТА ЗАЯВОК ДЛЯ УПРАВЛЯЮЩЕЙ КОМПАНИИ
Authors: ALEMASOV EVGENY , ZARIPOVA RIMMA
Published: March 2021

The article is devoted to the creation and application of the monitoring system, which will automatically collect and process requests from residents of houses to the dispatch services of their management companies, to control the process of execution of requests received and the effectiveness of the employees of the management company.
On the complex substantiation of the typology of juvenile delinquents: criminological and psychological aspect
Authors: Dushkin Anton , Suslov Yuriy , Shibaeva Galina
Published: March 2021

The article is devoted to the problem of juvenile delinquency, which is relevant in the context of discussing interdisciplinary issues of its prevention based on the analysis of the characteristics of the state of crime in the Russian Federation from 2018 to 2020. The article presents the content of psychological and legal categories that characterize the personality of a minor criminal and the mechanisms of the formation of criminal behavior. Special attention is paid to the description of the factors and conditions that contribute to the commission of crimes by minors, including repeated ones. On the example of specific classifications and typologies, the state of knowledge of the problem of studying the personality of a minor offender and a convicted person, as well as their psychological characteristics, is analyzed. The article describes the contribution of individual domestic and foreign scientists who proposed variants of classifications and typologies of juvenile delinquents.

The study found that a significant number of classifications and typologies of juvenile offenders often take as the basis of its system of one or more characteristics, research which largely depends on the scientific interests of the authors.

Based on the generalized scientific and empirical data on the psychological, criminological, socio-demographic characteristics of minors who have committed crimes, an attempt is made to typologize the designated group. As a result of the conducted research, priority areas of psychological and pedagogical work with minors in order to prevent crime were identified.
Scientific approaches in Russian and foreign psychology to study the crisis of professional development of the individual
Authors: Tkachenko Lyudmila , Kostina Lyubov'
Published: March 2021

The article is devoted to the theoretical analysis of the scientific views of domestic and foreign scientists on the crises of human development as a person and a subject of activity. The essential signs of a crisis of professional development are indicated - a difficult, difficult situation; a process consisting of external and internal contradictions that a person overcomes thanks to the socio-cultural environment and formed personal qualities. The factors of influence on the crisis of professional development, types and stages of crises of professional development, strategies of human behavior to overcome contradictions, as well as ways to overcome the crisis are highlighted. Special attention in scientific research is paid to crises that disorganize individual human behavior: at the beginning of the formation of an individual as a professional, in connection with entering a new work collective or its disintegration, at the stage of completing a professional career. The periods of development crises are characterized. The stages of the professional development crisis are revealed. Comparisons of scientific judgments about the crisis of professional development of domestic and foreign scientists-psychologists and ways of overcoming the development crisis are given. The conclusion is formulated that, in addition to the negative consequences of the crisis of professional development, there is also a positive result in the form of further development of the personality as a professional.
Features of conflicts of heads of internal affairs bodies and their manifestation in professional activities
Authors: Vahnina Viktoriya , Maltseva Tatyana
Published: March 2021

The authors reveal the psychological determinants of the constructive behavior of police officers in interpersonal conflicts with various categories of citizens, as well as the development of algorithms for psychologically competent actions of an employee in typical emotionally intense interpersonal situations.

In order to study the peculiarities of conflicts and their manifestations in the activities of the heads of the internal affairs bodies of the Russian Federation, an empirical study was carried out, in which 104 respondents took part - the heads of the territorial bodies of the internal affairs of the Russian Federation, both acting and temporarily undergoing training in various educational programs of the Academy. Department of the Ministry of Internal Affairs of Russia.

The study showed that modern chiefs of internal affairs bodies are focused on the implementation in everyday practice of interaction with subordinates of the subject-cooperating approach, since it is close to the national mentality and contributes to effective prevention and settlement of conflicts.

The most important task of the head of the internal affairs bodies in the process of managing socio-psychological conflicts is their objective complex analysis in order to use the positive experience of resolving conflicts and preventing the development of destructive socio-psychological conflicts.

The process of managing socio-psychological conflicts involves the implementation of modern psychotechnologies. To effectively solve emerging problems, each police officer must master the necessary minimum of theoretical knowledge and practical skills of behavior in a conflict, i.e. get conflictological training.
Promotion of road safety of the traffic police of the Ministry of internal Affairs of Russia among minors
Authors: Sklyarenko Inna , Sinicyna Olesya
Published: March 2021

In the introduction, the problem of road safety is updated, and especially, accidents and injuries of minors due to violations of traffic rules. In this connection, the need to optimize the promotion of road safety by the traffic police of the Ministry of internal Affairs of Russia among minors is becoming more acute. The purpose of this article is to substantiate the positive experience of the divisions of the traffic police Department of the Ministry of internal Affairs of Russia in Vologda in promoting road safety among minors of primary school age through a pedagogical study. The main part of the article offers a solution to the problem under consideration by forming an attitude to road safety among minors of primary school age. Based on the identified violations of traffic rules committed by minors of this age category, pedagogical principles are identified and tools for promoting road safety are selected. The organization of the activities of the traffic police inspector of the Ministry of internal Affairs of Russia on the basis of these principles and the corresponding pedagogical tools contributes to the formation of minors ' attitudes to road safety. The results of the study showed a positive impact of the selected pedagogical tools on the promotion of road safety among minors of primary school age corresponding to modern pedagogical principles. The article concludes with a General conclusion and practical recommendations based on the results of the study.
The influence of informatization on the systemic pedagogical traditions of the information and educational environment higher military education
Authors: Gubchenko Aleksey , Romanova Valeriya
Published: March 2021

The article examines the features of the influence of informatization on the systemic pedagogical traditions of military education in Russia. The authors believe that in the information and educational environment of military universities, under the influence of the introduction of elements of e-learning, information and information and communication educational technologies, there is a "partial" transformation of the traditional pedagogical system, which means its further functioning, taking into account the didactic innovations of electronic pedagogy and continuously improving information dangers , risks and threats in the global educational IT space.

The practice of informatization of the educational environment of the Military University and other military universities shows that due to the introduction and saturation of information and pedagogical methods of e-learning, IT and ICT educational technologies in the information and educational environment of military universities, a fundamental adjustment of the systemic pedagogical traditions of military educational institutions and the established reproductive -informative learning model

The renewal of the traditional pedagogical system comes into conflict and dangerous conflict with the "network" generation of "independent" learning content for an individual, whose consciousness, under the influence of the Internet, found itself in conditions of free access to universal knowledge, but at the same time completely without methodological, ideological, psychological, moral and political and legal conviction in its reliability, outside the philosophy of security and psychological protection.
Scalable Optimal Online Auctions
Authors: Coey Dominic , Larsen Bradley J. , Sweeney Kane , Waisman Caio
Published: March 2021

This paper provides a set of tools to compute and implement optimal reserve prices for online auctions.
Mechanism Design for Correlated Valuations: Efficient Methods for Revenue Maximization
Authors: Albert Michael , Conitzer Vincent , Lopomo Giuseppe , Stone Peter
Published: March 2021

Traditionally, much of the focus of the mechanism/auction design community has been on revenue optimal mechanisms for settings where bidders’ private valuations over outcomes can be reasonably thought of as independent of each other. This has been the case even though there is good reason to believe that valuations are often correlated and there are theoretical results suggesting that mechanisms designed with this correlation in mind can generate much higher revenue. In “Mechanism Design for Correlated Valuations: Efficient Methods for Revenue Maximization,” we look at the setting where there is correlation, but the exact distribution is unknown and must be estimated from samples. We show that in this setting, the previous extremely strong theoretical results around the usefulness of correlation are now very sensitive to the degree of correlation in the underlying distribution and the number of samples that the mechanism designer has access to. However, we also show that if correlation is sufficient, we can construct mechanisms, using a computationally efficient procedure, that significantly outperform traditional mechanism design paradigms.
Uncovering the Mitigating Psychological Response to Monitoring Technologies: Police Body Cameras Not Only Constrain but Also Depolarize
Authors: Patil Shefali V. , Bernstein Ethan S.
Published: March 2021

Despite organizational psychologists’ long-standing caution against monitoring (citing its reduction in employee autonomy and thus effectiveness), many organizations continue to use it, often with no detriment to performance and with strong support, not protest, from employees. We argue that a critical step to resolving this anomaly is revisiting researchers’ fundamental assumptions about access to gathered data. Whereas previous research assumes that access resides nearly exclusively with supervisors and other evaluators, technological advances have enabled employee access. We hypothesize that with employee access, the psychological effects of monitoring may be far more complex than previously acknowledged. Whereas multiparty access may still decrease employee autonomy, it may also trigger an important psychological benefit: alleviating employees’ perceptions of polarization—the increasing social and ideological divergence between themselves and their evaluators. Access gives employees unprecedented opportunities to use the “objective” footage to show others their perspective, address evaluators’ erroneous assumptions and stereotypes, and otherwise defuse ideological tensions. Lower perceived polarization, in turn, attenuates the negative effects that low autonomy would otherwise have on employee effectiveness. We find support for these hypotheses across three field studies conducted in the law enforcement context, which has been a trailblazer in using technological advances to grant broad access to multiple parties, including employees. Overall, our studies shed light on the conflicting (and ultimately more innocuous) impact of monitoring and encourage scholars to break from prior approaches to account for its increasing egalitarianism.
Adolescence: physical changes and neurological development
Authors: Best Olivia , Ban Sasha
Published: March 2021

This article provides a brief overview of adolescence. It highlights the key physical changes related to puberty and identifies the latest understanding of neurological development in young people. It is also recognised, within the article, that this period of rapid change can have an impact on social and emotional wellbeing. There are conditions that typically have an onset during adolescence, examples of this are offered. The term ‘adolescence’ is used to describe the stage of development and growth and ‘young people’ is used throughout to refer to the individuals.
We need to appreciate the nuances and make connections to outcomes
Authors: Hyde Robin L
Published: March 2021

Robin Hyde considers some of the anxieties around advanced practice and reflects on how to allay these
Introducing a flipped classroom in a pharmacology course
Authors: Sajjad Sehrish , Gowani Ambreen
Published: March 2021

Background:

Flipped classroom pedagogy has been shown to improve nursing students' academic performance.

Aim:

The study aimed to determine the effect of a flipped classroom approach on students' pharmacology assessment scores in a school of nursing in Karachi, Pakistan.

Methods:

A retrospective chart review was performed. The pharmacology test scores of the BSc nursing cohort of 2020, when flipped classroom pedagogy was used, was compared with those of the BSc nursing cohort of 2019, where traditional pedagogy was employed. Students' summative evaluation for the course and their verbal feedback were analysed.

Results:

The median continuous assessment test score of the 2019 cohort was 35 (interquartile range (IQR) 32–38), while that of the 2020 cohort was 38 (IQR 35–41). The difference in the score was statistically significant (P<0.001).

Conclusion:

The study gives an insight into a relatively novel pedagogy that was found to improve pharmacology knowledge test scores among nursing students.
Evaluation of the performance of covered lagoon digester in terms of the solids loading
Authors: Sousa Izabelle de Paula , Rosa André Pereira , Lopes Juciara Oliveira , Borges Alisson Carraro , Magos Baltzar dos Reis , Soares Matheus de Souza
Published: March 2021

The use of anaerobic digesters to convert residual biomass for energy use and nutrient recovery has been increasingly indicated by the operational simplicity and added value of the treatment by-products. However, the levels of solids present in the influents to be treated directly influence the operation and management of the system. Thus, the objective of the study was to evaluate the performance of covered lagoon digesters in terms of the solids loading in the swine wastewater treatment system. The study was performed in a farm located in Zona da Mata Mineira. The monitoring took place from September 2018 to August 2019. The influent flow of waste was estimated based on the analysis of monthly water consumption on the farm. The collection and sampling took place weekly, the influents and effuents were analyzed in terms of the solids loading of total solids (TS) and volatiles solids (VS). The mean total flow distributed to the two digesters was 102.3 m³.d-1, with a mean hydraulic retention time (HRT) of 24.5 days. The results ranged from 1.14 to 2.83% for TS at the start of treatment. In most of the monitored months, anaerobic digesters were being fed with organic overload in terms of VS, which consequently affected the efficiency of the system, which were 33.6% for TS and 39.5% for VS.
Spatial properties and propagation dynamics of apodized Hermite–Gauss beams
Authors: Boumeddine Ouis Chouaib , Bencheikh Abdelhalim , Chabou Saoussene
Published: March 2021

Hermite–Gauss beams (HGBs), which have been presented as exact solutions to the paraxial wave equation in Cartesian coordinates, are natural resonating modes in stable laser resonators. In this work, we demonstrate that the apodized Hermite–Gauss beam (ApHGB), by a decaying exponential functionexp⁡(γx)(γis the decaying or apodization parameter), is equivalent, under certain circumstances, to the apodized Airy beam (ApAiB). Based on the asymptotic treatment of the Hermite polynomials, we provide analytical expressions to describe their propagation dynamics in free space, then we investigate their similarity as a function of the apodization parameter. Moreover, by combining symmetric ApHGBs, we build dual and quad ApHGBs. The obtained numerical simulations confirm our analytical predictions. We believe that the ApHGB could be used as an alternative to the Airy beam in many applications.
Small footprint phase locking system for a large tiled aperture laser array
Authors: Boju A. , Maulion G. , Saucourt J. , Leval J. , Ledortz J. , Koudoro A. , Berthomier J.-M. , Naiim-Habib M. , Armand P. , Kermene V. , Desfarges-Berthelemot A. , Barthelemy A.
Published: March 2021

A phase sensing system fitted to the control of coherent laser beam array of large cross section is experimented. It is based on the use of a fiber bundle that collects a weak part of the synthetic wavefront, that scales it down (1/40) and that reshapes it in a more compact arrangement (2D to 1D array). Then, the reconfigured beam array can be analyzed by a small footprint system making the large laser beam array easier to phase-lock. The discrete laser array wavefront transmitted by the meter long fiber bundle was stabilized thanks to a multiple arm servo loop. Laser array phase locking was further ensured by random scattering through a diffuser, associated to an alternating projection algorithm. Six fiber laser beams constituting a 110 mm diameter synthetic aperture, were phase-locked with λ/16 accuracy.
Manipulating mode degeneracy for tunable spectral characteristics in multi-microcavity photonic molecules
Authors: Chen Jian , Hu Guangwei , Cao Guangtao , Deng Yan , Zhou Lei-ming , Wen Zhengji , Yang Hui , Li Guanhai , Chen Xiaoshuang
Published: March 2021

Optical microcavities are capable of confining light to a small volume, which could dramatically enhance the light-matter interactions and hence improve the performances of photonic devices. However, in the previous works on the emergent properties with photonic molecules composed of multiple plasmonic microcavities, the underlying physical mechanism is unresolved, thereby imposing an inevitable restriction on manipulating degenerate modes in microcavity with outstanding performance. Here, we demonstrate the mode-mode interaction mechanism in photonic molecules composed of degenerate-mode cavity and single-mode cavity through utilizing the coupled mode theory. Numerical and analytical results further elucidate that the introduction of direct coupling between the degenerate-mode cavity and single-mode cavity can lift the mode degeneracy and give rise to the mode splitting, which contributes to single Fano resonance and dual EIT-like effects in the double-cavity photonic molecule structure. Four times the optical delay time compared to typical double-cavity photonic molecule are achieved after removing the mode degeneracy. Besides, with the preserved mode degeneracy, ultra-wide filtering bandwidth and high peak transmission is obtained in multiple-cavity photonic molecules. Our results provide a broad range of applications for ultra-compact and multifunction photonic devices in highly integrated optical circuits.
Temperature-dependent radiative lifetime of Yb:YLF: refined cross sections and potential for laser cooling
Authors: Püschel Stefan , Kalusniak Sascha , Kränkel Christian , Tanaka Hiroki
Published: March 2021

We revisit the spectroscopic characterization of ytterbium-doped LiYF4 (Yb:YLF) for the application of laser cooling. Time-dependent fluorescence spectroscopy reveals a temperature dependence of the radiative lifetime which we explain by the Boltzmann distribution of excited ions in the upper Stark levels. The emission cross sections of Yb:YLF from 17 K to 440 K are revised using the temperature-dependent radiative lifetimes from fluorescence spectra. We provide fit equations for the peak values of important transitions as a function of temperature, which is also useful for the design of Yb:YLF laser oscillators and amplifiers operated at cryogenic temperatures. Based on our spectroscopic data, we show the prerequisite crystal purity to achieve laser cooling below liquid nitrogen temperatures.
Quantum-enhanced two-photon spectroscopy using two-mode squeezed light
Authors: Prajapati Nikunjkumar , Niu Ziqi , Novikova Irina
Published: March 2021

We investigate the prospects of using two-mode intensity squeezed twin beams, generated in Rb vapor, to improve the sensitivity of spectroscopic measurements by engaging two-photon Raman transitions. As a proof-of-principle demonstration, we recorded quantum-enhanced measurements of the Rb5D3/2hyperfine structure with reduced requirements for the Raman pump laser power and Rb vapor number density.
Behavior of dicentric chromosomes in budding yeast
Authors: Cook Diana , Long Sarah , Stanton John , Cusick Patrick , Lawrimore Colleen , Yeh Elaine , Grant Sarah , Bloom Kerry
Published: March 2021

DNA double-strand breaks arisein vivowhen a dicentric chromosome (two centromeres on one chromosome) goes through mitosis with the two centromeres attached to opposite spindle pole bodies. Repair of the DSBs generates phenotypic diversity due to the range of monocentric derivative chromosomes that arise. To explore whether DSBs may be differentially repaired as a function of their spatial position in the chromosome, we have examined the structure of monocentric derivative chromosomes from cells containing a suite of dicentric chromosomes in which the distance between the two centromeres ranges from 6.5 kb to 57.7 kb. Two major classes of repair products, homology-based (homologous recombination (HR) and single-strand annealing (SSA)) and end-joining (non-homologous (NHEJ) and micro-homology mediated (MMEJ)) were identified. The distribution of repair products varies as a function of distance between the two centromeres. Genetic dependencies on double strand break repair (Rad52), DNA ligase (Lif1), and S phase checkpoint (Mrc1) are indicative of distinct repair pathway choices for DNA breaks in the pericentromeric chromatin versus the arms.
Association of genetic liability to smoking initiation with e-cigarette use in young adults: A cohort study
Authors: Khouja Jasmine N. , Wootton Robyn E. , Taylor Amy E. , Davey Smith George , Munafò Marcus R.
Published: March 2021

Background

Tobacco smoking and e-cigarette use are strongly associated, but it is currently unclear whether this association is causal, or due to shared factors that influence both behaviours such as a shared genetic liability. The aim of this study was to investigate whether polygenic risk scores (PRS) for smoking initiation are associated with ever use of e-cigarettes.

Methods and findings

Smoking initiation PRS were calculated for young adults (N = 7,859, mean age = 24 years, 51% male) of European ancestry in the Avon Longitudinal Study of Parents and Children, a prospective birth cohort study initiated in 1991. PRS were calculated using the GWAS & Sequencing Consortium of Alcohol and Nicotine use (GSCAN) summary statistics. Five thresholds ranging from 5 × 10−8 to 0.5 were used to calculate 5 PRS for each individual. Using logistic regression, we investigated the association between smoking initiation PRS and the main outcome, self-reported e-cigarette use (n = 2,894, measured between 2016 and 2017), as well as self-reported smoking initiation and 8 negative control outcomes (socioeconomic position at birth, externalising disorders in childhood, and risk-taking in young adulthood). A total of 878 young adults (30%) had ever used e-cigarettes at 24 years, and 150 (5%) were regular e-cigarette users at 24 years. We observed positive associations of similar magnitude between smoking initiation PRS (created using the p < 5 × 10−8 threshold) and both smoking initiation (odds ratio (OR) = 1.29, 95% CI 1.19 to 1.39, p < 0.001) and ever e-cigarette use (OR = 1.24, 95% CI 1.14 to 1.34, p < 0.001) by the age of 24 years, indicating that a genetic predisposition to smoking initiation is associated with an increased risk of using e-cigarettes. At lower p-value thresholds, we observed an association between smoking initiation PRS and ever e-cigarette use among never smokers. We also found evidence of associations between smoking initiation PRS and some negative control outcomes, particularly when less stringent p-value thresholds were used to create the PRS, but also at the strictest threshold (e.g., gambling, number of sexual partners, conduct disorder at 7 years, and parental socioeconomic position at birth). However, this study is limited by the relatively small sample size and potential for collider bias.

Conclusions

Our results indicate that there may be a shared genetic aetiology between smoking and e-cigarette use, and also with socioeconomic position, externalising disorders in childhood, and risky behaviour more generally. This indicates that there may be a common genetic vulnerability to both smoking and e-cigarette use, which may reflect a broad risk-taking phenotype.
Zika-related adverse outcomes in a cohort of pregnant women with rash in Pernambuco, Brazil
Authors: Ximenes Ricardo Arraes de Alencar , Miranda-Filho Demócrito de Barros , Montarroyos Ulisses Ramos , Martelli Celina Maria Turchi , Araújo Thalia Velho Barreto de , Brickley Elizabeth , Albuquerque Maria de Fátima Pessoa Militão de , Souza Wayner Vieira , Ventura Liana O. , Ventura Camila V. , Gois Adriana L. , Leal Mariana C. , Oliveira Danielle Maria da Silva , Eickmann Sophie Helena , Carvalho Maria Durce C. G. , Silva Paula F. S. da , Rocha Maria Angela Wanderley , Ramos Regina Coeli Ferreira , Brandão-Filho Sinval Pinto , Cordeiro Marli Tenorio , Bezerra Luciana Caroline Albuquerque , Dimech George , Valongueiro Sandra , Pires Pedro , Castanha Priscila Mayrelle da Silva , Dhalia Rafael , Marques-Júnior Ernesto Torres Azevedo , Rodrigues Laura C. ,   on behalf of the Microcephaly Epidemic Research Group (MERG)
Published: March 2021

Background

While Zika virus (ZIKV) is now widely recognized as a teratogen, the frequency and full spectrum of adverse outcomes of congenital ZIKV infection remains incompletely understood.

Methods

Participants in the MERG cohort of pregnant women with rash, recruited from the surveillance system from December/2015-June/2017. Exposure definition was based on a combination of longitudinal data from molecular, serologic (IgM and IgG3) and plaque reduction neutralization tests for ZIKV. Children were evaluated by a team of clinical specialists and by transfontanelle ultrasound and were classified as having microcephaly and/or other signs/symptoms consistent with congenital Zika syndrome (CZS). Risks of adverse outcomes were quantified according to the relative evidence of a ZIKV infection in pregnancy.

Findings

376 women had confirmed and suspected exposure to ZIKV. Among evaluable children born to these mothers, 20% presented with an adverse outcome compatible with exposure to ZIKV during pregnancy. The absolute risk of microcephaly was 2.9% (11/376), of calcifications and/or ventriculomegaly was 7.2% (13/180), of additional neurologic alterations was 5.3% (13/245), of ophthalmologic abnormalities was 7% (15/214), and of dysphagia was 1.8% (4/226). Less than 1% of the children experienced abnormalities across all of the domains simultaneously. Interpretation: Although approximately one-fifth of children with confirmed and suspected exposure to ZIKV in pregnancy presented with at least one abnormality compatible with CZS, the manifestations presented more frequently in isolation than in combination. Due to the rare nature of some outcomes and the possibility of later manifestations, large scale individual participant data meta-analysis and the long-term evaluation of children are imperative to identify the full spectrum of this syndrome and to plan actions to reduce damages.
High initial IgG antibody levels against Orientia tsutsugamushi are associated with an increased risk of severe scrub typhus infection
Authors: Devamani Carol S. , Prakash John A. J. , Alexander Neal , Stone William , Gunasekaran Karthik , Rose Winsley , Schmidt Wolf-Peter
Published: March 2021

Background

Scrub typhus is a dominant cause of febrile illness in many parts of Asia. Immunity is limited by the great strain diversity of Orientia tsutsugamushi. It is unclear whether previous infection protects from severe infection or enhances the risk.

Methods/principal findings

We studied IgG antibody levels against O. tsutsugamushi at presentation in 636 scrub typhus patients using enzyme-linked immunosorbent assays (ELISA). The association between ELISA optical density (OD) and risk of severe infection was modelled using Poisson regression. OD was categorised as low (<1.0), intermediate (1.0 to 2.9), and high (≥3.0). OD was also modelled as a continuous variable (cubic spline). Median age of cases was 41 years (range 0–85), with 37% having severe infection. Compared to the low category, the age-adjusted risk of severe infection was 1.5 times higher in the intermediate category (95%CI 1.2, 1.9), and 1.3 times higher in the high category (95%CI 1.0, 1.7). The effect was stronger in cases <40 years, doubling the risk in the intermediate and high categories compared to the low category. The effect was more pronounced in cases tested within 7 days of fever onset when IgG ODs are more likely to reflect pre-infection levels.

Conclusions/Significance

Intermediate and high IgG antibody levels at the time of diagnosis are associated with a higher risk of severe scrub typhus infection. The findings may be explained by severe infection eliciting an accelerated IgG response or by previous scrub typhus infection enhancing the severity of subsequent episodes.
Ultra-precise quantification of mRNA targets across a broad dynamic range with nanoreactor beads
Authors: Loncarevic Ivan Francisco , Toepfer Susanne , Hubold Stephan , Klingner Susanne , Kanitz Lea , Ellinger Thomas , Steinmetzer Katrin , Ernst Thomas , Hochhaus Andreas , Ermantraut Eugen
Published: March 2021

Precise quantification of molecular targets in a biological sample across a wide dynamic range is a key requirement in many diagnostic procedures, such as monitoring response to therapy or detection of measurable residual disease. State of the art digital PCR assays provide for a dynamic range of four orders of magnitude. However digital assays are complex and require sophisticated microfluidic tools. Here we present an assay format that enables ultra-precise quantification of RNA targets in a single measurement across a dynamic range of more than six orders of magnitude. The approach is based on hydrogel beads that provide for microfluidic free compartmentalization of the sample as they are used as nanoreactors for reverse transcription, PCR amplification and combined real time and digital detection of gene transcripts. We have applied these nanoreactor beads for establishing an assay for the detection and quantification of BCR-ABL1 fusion transcripts. The assay has been characterized for its precision and linear dynamic range. A comparison of the new method against conventional real time RT-PCR analysis (reference method) with clinical samples from patients with chronic myeloid leukemia (CML) revealed excellent concordance with Pearsons correlation coefficient of 0.983 and slope of 1.08.
Explaining the effective reproduction number of COVID-19 through mobility and enterprise statistics: Evidence from the first wave in Japan
Authors: Kajitani Yoshio , Hatayama Michinori
Published: March 2021

This study uses mobility statistics combined with business census data for the eight Japanese prefectures with the highest coronavirus disease-2019 (COVID-19) infection rates to study the effect of mobility reductions on the effective reproduction number (i.e., the average number of secondary cases caused by one infected person). Mobility statistics are a relatively new data source created by compiling smartphone location data; they can be effectively used for understanding pandemics if integrated with epidemiological findings and other economic data sets. Based on data for the first wave of infections in Japan, we found that reductions targeting the hospitality industry were slightly more effective than restrictions on general business activities. Specifically, we found that to hold back the pandemic (that is, to reduce the effective reproduction number to one or less for all days), a 20%–35% reduction in weekly mobility is required, depending on the region. A lesser goal, 80% of days with one or less observed transmission, can be achieved with a 6%–30% reduction in weekly mobility. These are the results if other potential causes of spread are ignored; for a fuller picture, more careful observations, expanded data sets, and advanced statistical modeling are needed.
Deletion of arginase 2 attenuates neuroinflammation in an experimental model of optic neuritis
Authors: Candadai Amritha A. , Liu Fang , Fouda Abdelrahman Y. , Alfarhan Moaddey , Palani Chithra D. , Xu Zhimin , Caldwell Ruth B. , Narayanan S. Priya
Published: March 2021

Vision impairment due to optic neuritis (ON) is one of the major clinical presentations in Multiple Sclerosis (MS) and is characterized by inflammation and degeneration of the optic nerve and retina. Currently available treatments are only partially effective and have a limited impact on the neuroinflammatory pathology of the disease. A recent study from our laboratory highlighted the beneficial effect of arginase 2 (A2) deletion in suppressing retinal neurodegeneration and inflammation in an experimental model of MS. Utilizing the same model, the present study investigated the impact of A2 deficiency on MS-induced optic neuritis. Experimental autoimmune encephalomyelitis (EAE) was induced in wild-type (WT) and A2 knockout (A2-/-) mice. EAE-induced cellular infiltration, as well as activation of microglia and macrophages, were reduced in A2-/- optic nerves. Axonal degeneration and demyelination seen in EAE optic nerves were observed to be reduced with A2 deletion. Further, the lack of A2 significantly ameliorated astrogliosis induced by EAE. In conclusion, our findings demonstrate a critical involvement of arginase 2 in mediating neuroinflammation in optic neuritis and suggest the potential of A2 blockade as a targeted therapy for MS-induced optic neuritis.
On the influence of cell shape on dynamic reaction-diffusion polarization patterns
Authors: Eroumé K. , Vasilevich A. , Vermeulen S. , de Boer J. , Carlier A.
Published: March 2021

The distribution of signaling molecules following mechanical or chemical stimulation of a cell defines cell polarization, with regions of high active Cdc42 at the front and low active Cdc42 at the rear. As reaction-diffusion phenomena between signaling molecules, such as Rho GTPases, define the gradient dynamics, we hypothesize that the cell shape influences the maintenance of the “front-to-back” cell polarization patterns. We investigated the influence of cell shape on the Cdc42 patterns using an established computational polarization model. Our simulation results showed that not only cell shape but also Cdc42 and Rho-related (in)activation parameter values affected the distribution of active Cdc42. Despite an initial Cdc42 gradient, the in silico results showed that the maximal Cdc42 concentration shifts in the opposite direction, a phenomenon we propose to call “reverse polarization”. Additional in silico analyses indicated that “reverse polarization” only occurred in a particular parameter value space that resulted in a balance between inactivation and activation of Rho GTPases. Future work should focus on a mathematical description of the underpinnings of reverse polarization, in combination with experimental validation using, for example, dedicated FRET-probes to spatiotemporally track Rho GTPase patterns in migrating cells. In summary, the findings of this study enhance our understanding of the role of cell shape in intracellular signaling.
Blind deconvolution estimation by multi-exponential models and alternated least squares approximations: Free-form and sparse approach
Authors: Campos-Delgado Daniel U. , Gutierrez-Navarro Omar , Salinas-Martinez Ricardo , Duran Elvis , Mejia-Rodriguez Aldo R. , Velazquez-Duran Miguel J. , Jo Javier A.
Published: March 2021

The deconvolution process is a key step for quantitative evaluation of fluorescence lifetime imaging microscopy (FLIM) samples. By this process, the fluorescence impulse responses (FluoIRs) of the sample are decoupled from the instrument response (InstR). In blind deconvolution estimation (BDE), the FluoIRs and InstR are jointly extracted from a dataset with minimal a priori information. In this work, two BDE algorithms are introduced based on linear combinations of multi-exponential functions to model each FluoIR in the sample. For both schemes, the InstR is assumed with a free-form and a sparse structure. The local perspective of the BDE methodology assumes that the characteristic parameters of the exponential functions (time constants and scaling coefficients) are estimated based on a single spatial point of the dataset. On the other hand, the same exponential functions are used in the whole dataset in the global perspective, and just the scaling coefficients are updated for each spatial point. A least squares formulation is considered for both BDE algorithms. To overcome the nonlinear interaction in the decision variables, an alternating least squares (ALS) methodology iteratively solves both estimation problems based on non-negative and constrained optimizations. The validation stage considered first synthetic datasets at different noise types and levels, and a comparison with the standard deconvolution techniques with a multi-exponential model for FLIM measurements, as well as, with two BDE methodologies in the state of the art: Laguerre basis, and exponentials library. For the experimental evaluation, fluorescent dyes and oral tissue samples were considered. Our results show that local and global perspectives are consistent with the standard deconvolution techniques, and they reached the fastest convergence responses among the BDE algorithms with the best compromise in FluoIRs and InstR estimation errors.