bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of glycosylation and disulfide bonding of wild-type SARS-CoV-2 spike glycoprotein
Authors: Zhang Shijian , Go Eden P. , Ding Haitao , Anang Saumya , Kappes John C. , Desaire Heather , Sodroski Joseph
Published: April 2021

The SARS-CoV-2 coronavirus, the etiologic agent of COVID-19, uses its spike (S) glycoprotein anchored in the viral membrane to enter host cells. The S glycoprotein is the major target for neutralizing antibodies elicited by natural infection and by vaccines. Approximately 35% of the SARS-CoV-2 S glycoprotein consists of carbohydrate, which can influence virus infectivity and susceptibility to antibody inhibition. We found that virus-like particles produced by coexpression of SARS-CoV-2 S, M, E and N proteins contained spike glycoproteins that were extensively modified by complex carbohydrates. We used a fucose-selective lectin to enrich the Golgi-resident fraction of a wild-type SARS-CoV-2 S glycoprotein trimer, and determined its glycosylation and disulfide bond profile. Compared with soluble or solubilized S glycoproteins modified to prevent proteolytic cleavage and to retain a prefusion conformation, more of the wild-type S glycoprotein N-linked glycans are processed to complex forms. Even Asn 234, a significant percentage of which is decorated by high-mannose glycans on soluble and virion S trimers, is predominantly modified in the Golgi by processed glycans. Three incompletely occupied sites of O-linked glycosylation were detected. Viruses pseudotyped with natural variants of the serine/threonine residues implicated in O-linked glycosylation were generally infectious and exhibited sensitivity to neutralization by soluble ACE2 and convalescent antisera comparable to that of the wild-type virus. Unlike other natural cysteine variants, a Cys15Phe (C15F) mutant retained partial, but unstable, infectivity. These findings enhance our understanding of the Golgi processing of the native SARS-CoV-2 S glycoprotein carbohydrates and could assist the design of interventions.
Global ubiquitylation analysis of mitochondria in primary neurons identifies physiological Parkin targets following activation of PINK1
Authors: Antico Odetta , Ordureau Alban , Stevens Michael , Singh Francois , Gierlinski Marek , Barini Erica , Rickwood Mollie L. , Prescott Alan , Toth Rachel , Ganley Ian G. , Harper J. Wade , Muqit Miratul M. K.
Published: April 2021

Autosomal recessive mutations in PINK1 and Parkin cause Parkinson’s disease. How activation of PINK1 and Parkin leads to elimination of damaged mitochondria by mitophagy is largely based on cell culture studies with few molecular studies in neurons. Herein we have undertaken a global proteomic-analysis of mitochondria from mouse neurons to identify ubiquitylated substrates of endogenous Parkin activation. Comparative analysis with human iNeuron datasets revealed a subset of 49 PINK1-dependent diGLY sites upregulated upon mitochondrial depolarisation in 22 proteins conserved across mouse and human systems. These proteins were exclusively localised at the mitochondrial outer membrane (MOM) including, CISD1, CPT1α, ACSL1, and FAM213A. We demonstrate that these proteins can be directly ubiquitylated by Parkinin vitro. We also provide evidence for a subset of cytoplasmic proteins recruited to mitochondria that undergo PINK1 and Parkin independent ubiquitylation including SNX3, CAMK2α and CAMK2β indicating the presence of alternate ubiquitin E3 ligase pathways that are activated by mitochondrial depolarisation in neurons. Finally we have developed an online resource to visualise mitochondrial ubiquitin sites in neurons and search for ubiquitin components recruited to mitochondria upon mitochondrial depolarisation, MitoNUb. This analysis will aid in future studies to understand Parkin activation in neuronal subtypes. Our findings also suggest that monitoring ubiquitylation status of the 22 identified MOM proteins may represent robust biomarkers for PINK1 and Parkin activityin vivo.
Expanding Asgard members in the domain of Archaea shed new light on the origin of eukaryotes
Authors: Xie Ruize , Wang Yinzhao , Huang Danyue , Hou Jialin , Li Liuyang , Hu Haining , Zhao Xiaoxiao , Wang Fengping
Published: April 2021

The hypothesis that eukaryotes originated from within the domain Archaea has been strongly supported by recent phylogenomic analyses placing Heimdallarchaeota from the Asgard superphylum as the closest known archaeal sister-group to eukaryotes. At present, only six phyla are described in the Asgard superphylum, which limits our understanding of the relationship between eukaryotes and archaea, as well as the evolution and ecological functions of the Asgard archaea. Here, we describe five previously unknown phylum-level Asgard archaeal lineages, tentatively named Tyr-, Sigyn-, Freyr-, Njord- and Balderarchaeota. Comprehensive phylogenomic analyses further supported the origin of eukaryotes within Archaea and a new Asgard lineage Njordarchaeota was supposed as the known closest branch with the eukaryotic nuclear host lineage. Metabolic reconstruction suggests that the Asgard archaea described here have potential to fix inorganic carbon via the Wood-Ljungdahl pathway and degrade organic matters except Njordarchaeota, which may possess a heterotrophic lifestyle with capability of peptides and amino acids utilization. Additionally, the Ack/Pta pathway for homoacetogenesis andde novoanaerobic cobalamin biosynthesis pathway were found in Balderarchaeota and Tyrarchaeota, respectively. This study largely expands the Asgard superphylum, provides additional evidences to support the 2-domain life tree and sheds new light on the evolution of eukaryotes.
Non-parametric synergy modeling with Gaussian processes
Authors: Shapovalova Yuliya , Heskes Tom , Dijkstra Tjeerd
Published: April 2021

Background

Understanding the synergetic and antagonistic effects of combinations of drugs and toxins is vital for many applications, including treatment of multifactorial diseases and ecotoxicological monitoring. Synergy is usually assessed by comparing the response of drug combinations to a predicted non-interactive response from reference (null) models. Possible choices of null models are Loewe additivity, Bliss independence and the recently rediscovered Hand model. A different approach is taken by the MuSyC model, which directly fits a generalization of the Hill model to the data. All of these models, however, fit the dose-response relationship with a parametric model.

Results

We propose the Hand-GP model, a non-parametric model based on the combination of the Hand model with Gaussian processes. We introduce a new logarithmic squared exponential kernel for the Gaussian process which captures the logarithmic dependence of response on dose. From the monotherapeutic response and the Hand principle, we construct a null reference response and synergy is assessed from the difference between this null reference and the Gaussian process fitted response. We evaluated performance of our model on a simulated data from Greco, two simulated data sets of our own design and two benchmark data sets from Chou and Talalay. We compare the Hand-GP model to standard synergy models and show that our model performs better than these standards. We also compare our model to the MuSyC model as example of a recent method which also fits a complete dose-response surface. Also in this case, the Hand-GP model performs better.

Conclusion

The Hand-GP model is a flexible model to capture synergy. Its non-parametric natures allows it to model a wide variety of response patterns.
The interplay between growth rate and nutrient quality defines gene expression capacity
Authors: Kim Juhyun , Darlington Alexander P.S. , Bates Declan G. , Jimenez Jose I.
Published: April 2021

The gene expression capacity of bacterial cells depends on the interplay between growth and the availability of the transcriptional and translational machinery. Growth rate is widely accepted as the global physiological parameter controlling the allocation of cell resources. This allocation has an impact on the ability of the cell to produce both host and heterologous proteins required for synthetic circuits and pathways. Understanding the relationship between growth and resources is key for the efficient design of artificial genetic constructs, however, it is obscured by the mutual dependence of growth and gene expression on each other. In this work, we investigate the individual contributions of molecular factors, growth rate and metabolism to gene expression by investigating the behaviour of bacterial cells growing in chemostats in growth-limited conditions. We develop a model of the whole cell that captures trade-offs in gene expression arising from the individual contributions of different factors, and validate it by analysing gene couplings which emerge from competition for the gene expression machinery. Our results show that while growth rate and molecular factors, such as the number of rRNA operons, set the abundance of transcriptional and translational machinery available, it is metabolism that governs the usage of those resources by tuning elongation rates. We show that synthetic gene expression capacity can be maximised by using low growth in a high-quality medium. These findings provide valuable insights into fundamental trade-offs in microbial physiology that will inform future strain and bioprocesses optimisation.
Optimized sample selection for cost-efficient long-read population sequencing
Authors: Ranallo-Benavidez T. Rhyker , Lemmon Zachary , Soyk Sebastian , Aganezov Sergey , Salerno William J. , McCoy Rajiv C. , Lippman Zachary B. , Schatz Michael C. , Sedlazeck Fritz J.
Published: April 2021

An increasingly important scenario in population genetics is when a large cohort has been genotyped using a low-resolution approach (e.g., microarrays, exome capture, short-read WGS), from which a few individuals are resequenced using a more comprehensive approach, especially long-read sequencing. The subset of individuals selected should ensure that the captured genetic diversity is fully representative and includes variants across all subpopulations. For example, human variation has historically focused on individuals with European ancestry, but this represents a small fraction of the overall diversity. Addressing this, SVCollector identifies the optimal subset of individuals for resequencing by analyzing population-level VCF files from low-resolution genotyping studies. It then computes a ranked list of samples that maximizes the total number of variants present within a subset of a given size. To solve this optimization problem, SVCollector implements a fast, greedy heuristic and an exact algorithm using integer linear programming. We apply SVCollector on simulated data, 2504 human genomes from the 1000 Genomes Project, and 3024 genomes from the 3000 Rice Genomes Project and show the rankings it computes are more representative than alternative naive strategies. When selecting an optimal subset of 100 samples in these cohorts, SVCollector identifies individuals from every subpopulation, whereas naive methods yield an unbalanced selection. Finally, we show the number of variants present in cohorts selected using this approach follows a power-law distribution that is naturally related to the population genetic concept of the allele frequency spectrum, allowing us to estimate the diversity present with increasing numbers of samples.
Consumer appreciation of a shark-free eco-label for small pelagics
Authors: Mulazzani Luca , Piredda Laura , Cerjak Marija , Camanzi Luca
Published: April 2021

Purpose

The objective of this study is to assess if Italian fish consumers are sensible to shark protection and if they would contribute paying more for small pelagic fishes coming from fisheries that are certified as “shark-free”.

Design/methodology/approach

Contingent valuation is used to estimate willingness to pay with a double approach, including a dichotomous choice and an open-ended question. Inconsistency between the two answers is allowed. This allows the correction of two sources of bias (i.e. preference uncertainty and anchoring effect) and has permitted that the two estimation methods converged to the same result.

Findings

Consumers show interest for the “shark-free” label. Premium price is estimated at +26%. Variables affecting willingness to pay (WTP) in the sample are age, income, environmental attitude, knowledge of organic labels and frequency of small pelagics' consumption. Results need to be confirmed by a replication on a larger (probabilistic) sample and with a different distribution of bids.

Originality/value

Ecosystems provide different benefits to humankind, including non-use services, such as the satisfaction to know that a species is well conserved. Generally, appreciation is higher for what are considered charismatic species. In this paper, the authors investigate if sharks can be considered charismatic species despite their “bad reputation”. The interest in shark survival is measured indirectly using a “shark-free” label on a commercial species like anchovy, allowing to increase the value added of this low-price species.
Key determinants of quality in the pharmaceutical supply chain
Authors: Tayyab Muhammad , Awan Muhammad Usman , Bukhari Nadeem Irfan , Sabet Ehsan
Published: April 2021

Purpose

Empirical studies on the supply chain quality management (SCQM) of the pharmaceutical sector are scarce and scattered. This paper investigates a set of key quality determinants in the pharmaceutical sector to offer a holistic quality control framework for its supply chain (SC).

Design/methodology/approach

A mixed-method design was used. A focused group discussion with seven pharmaceutical SC managers summarized the narratives of the SCQM in this sector and helped to develop a questionnaire. The survey data were collected from the managers of 299 pharmaceutical firms.

Findings

The statistical results show the key determinants are leadership (LS), customer focus (CF), process integration and management (PIM), supplier relations (SR), quality practice (QP), human resource practices (HRP) and safety (SF). Unlike many other sectors, in the pharmaceutical SC, logistics and inventory costs have been proved to be not as important as other measures in the eyes of the SC managers and as part of SCQM performance measures, which can be a result of the priority systems influenced by the World Health Organization standards.

Originality/value

The study is distinctive in its scope as is carried out in a developing country with focus on concept of SCQM with reference to pharmaceutical SC. It shows great potential for further studies and improvements in logistics and warehousing in this sector, for the interest of the pharmaceutical SC managers and regulators who aim to ensure safety and quality in the health-care sector.
Emotional intelligence and perceived organizational support as predictors of emotional exhaustion among nurses and midwives
Authors: Lartey Joshua King Safo , Amponsah-Tawiah Kwesi , Osafo Joseph
Published: April 2021

Purpose

Navigating the physical and emotional conditions of patients on daily basis can be emotionally exhaustive, requiring health professional to regulate their emotions in order to provide quality healthcare. The present study set out to examine the consequential effect of emotional intelligence and perceived organizational support (POS) on emotional exhaustion of nurses and midwives in the Ghanaian context. The study also examined the effects of age and cadres of nursing and midwifery on emotional exhaustion.

Design/methodology/approach

The study was quantitative in nature and employed the cross-sectional design in sampling respondents. The study was conducted in four public hospitals and two quasi-public hospitals in three main districts in the Greater Accra Region of Ghana. A sample of 342 nurses and midwives were proportionately sampled from various health facilities. The sample constituted of staff nurses and midwives.

Findings

The study revealed that while age, cadres of nursing and midwifery and POS had consequential effects on emotional exhaustion, emotional intelligence failed to predict emotional exhaustion.

Originality/value

Findings of the study draw the attention to the importance of organizational support in attenuating the emotional exhaustion associated with the nursing profession.
(In)effective leadership? Exploring the interplay of challenges, goals and measures in the context of school improvement
Authors: Böse Susanne , Brauckmann-Sajkiewicz Stefan
Published: April 2021

Purpose

This study aims to explore the extent to which schools principals serving disadvantaged communities in Germany are able to set appropriate goals and choose suitable measures for improving their schools according to the specific challenges they face. The authors determine whether principals are able to identify their schools' challenges or whether they merely follow “universal recipes” of the school effectiveness research paradigm regardless of their particular school context. This effectiveness-driven accountability approach requires an in-depth evaluation of the school and its stakeholders and might lead to a new attitude toward failure that sees it as an essential part of developing effective school improvement plans.

Design/methodology/approach

The authors conducted descriptive and correlative analyses as well as exploratory and confirmatory factor analyses using longitudinal data of 164 school principals. Through cross-sectional analyses, the authors investigated the connection among challenges, goals and measures and how they correlated with (self-reported) improvements.

Findings

From a leadership perspective, priorities for school improvement should be aligned with the school-specific challenges they identify and the goals they set to address them.

Research limitations/implications

The extent to which legislation concerning individual school quality development programs can translate into feasible and effective actions is unclear. Caution should be taken when interpreting the findings of this study, as they reflect school principals' self-selected evaluation measures and therefore might be biased.

Practical implications

In future research, emphasis should be placed on school management processes, in particular, the development of strategic decision-making, structuring of target perspectives and derivation of steps in school improvement and instructional development. The authors recommend the government offer school principals appropriate and adequate training and support services to prevent them from overburdening their staff.

Originality/value

This paper contributes to a deeper understanding of processes concerning strategic leadership, as opposed to operative management, of schools by revealing context-sensitive considerations.
Relationship of perceived supervisor support, self-efficacy and turnover intention, the mediating role of burnout
Authors: Chami-Malaeb Rola
Published: April 2021

Purpose

The purpose of this paper is to study the effect of two positive organizational factors: the perceived supervisor support (PSS) and the self-efficacy (SE) on nurses' burnout (BO), which concurrently affect the turnover intention (TI) and the mediating role of BO in this relationship.

Design/methodology/approach

A cross-sectional survey-based study of a sample of 552 Lebanese registered nurses from 19 Lebanese hospitals was conducted.

Findings

The authors’ findings confirm that PSS and SE both reduce the level of BO and the turnover intention significantly. The higher the perceived supervisors' support and the nurses' SE, the less they experience BO. BO has partially mediated the relationship of the PSS and SE on TI. This study reveals that supervisors' support is well perceived by Lebanese nurses, whose s is relatively high, while their levels of BO are considered moderate. However, BO levels vary proportionally with demographic variables, namely age, work experience, gender, marital status and education.

Originality/value

This study provides new evidence on the relationship between PSS, SE and BO and turnover intention of Lebanese nurses. It is unique in studying the role of nurses' SE with regard to BO and TI and improving the quality of nurses' work life. It shows the significance of the supervisors' role in supporting the psychological state of nurses. The context of the study, Lebanon, is also novel as it differs from advanced economies institutionally, culturally and in legal frameworks that govern the employee–supervisor relationships.
A narrative review of reviews of interconnecting risks (IR) of mental health problems for young people
Authors: Edbrooke‐Childs Julian , Deighton Jessica
Published: April 2021

The aim of this narrative review is to examine the most prevalent multiple or interconnecting risks of mental health problems that have been identified in previous reviews of the literature and to examine those most prevalent for children and young people. Overall, ten databases were searched for published literature reviews, and from 1,556 unique hits, 91 reviews examining individual risks were included, with 35 reviews examining interconnecting risks. The findings suggest that interpersonal connection plays a central role in interconnecting risks, as indicated by the number of interconnections between social groups, interpersonal, parental relationships and family cohesion with other risk themes. Family and systemic approaches have clear value in supporting young people by enabling the development of a secure relational foundation on which to build future protective interpersonal connections.

Practitioner Points

Interpersonal connection plays a central role in interconnecting risks, as indicated by the number of interconnections between social groups, interpersonal, parental relationships and family cohesion with other risk themes.

Interventions that support young people to build and maintain interpersonal connections when experiencing individual and interconnecting risks may have important consequences for the prevention and early intervention of mental health problems.

Family and systemic approaches have clear value in supporting young people by enabling the development of a secure relational foundation on which to build future protective interpersonal connections.
Exploring subjective experiences of international social workers in Asia: Content analysis of Japanese field reports
Authors: Higashida Masateru
Published: April 2021

The aim of this study is to explore the subjective and practical experiences of international social workers, focusing on the content, outcomes, impact, and related factors of their activities in Asia. Individual reports of social workers dispatched from Japan to 11 Asian countries during the period of 2003–2018 were collected (n = 59). A mixed quantitative and qualitative content analysis was used to examine their experiences and perceptions in the field. Parts of their reports were categorized mainly into the relationship between requested activities and perceived needs, the type of social work activities conducted, experiences of success and failure in activities, and perceived outcomes and impact of the activities. The quantitative analysis showed that approximately 48.9% of the social workers described positive outcomes of their activities and 43.9% described positive impacts of their activities on the placement or communities. The qualitative analysis revealed that they experienced a variety of difficulties, together with sociocultural and religious differences. Many of their experiences of success or failure appeared to be associated with their interactions with local stakeholders. The findings suggest the importance of the reflective and contextualized practice of international developmental social workers with local stakeholders.
Component‐resolved diagnosis using guinea‐pig allergens elucidates allergen sensitization profiles in allergy to furry animals
Authors: Swiontek Kyra , Kler Stéphanie , Lehners Christiane , Ollert Markus , Hentges François , Hilger Christiane
Published: April 2021

Background

Furry animals are an important source of indoor allergens. Diagnosis of allergy to small pets such as guinea‐pigs still relies on animal dander extracts which do not allow to define the primary sensitization source.

Objective

To identify major guinea‐pig allergens and to evaluate their potential as marker allergens for in vitro IgE‐diagnosis in comparison with dander extracts.

Methods

A group of patients allergic to guinea‐pig (n = 29) and a group of patients allergic to cat and dog (n = 30) were recruited for the study. A panel of four guinea‐pig lipocalin allergens was expressed as recombinant proteins in E. coli. Specific IgE were quantified by ImmunoCAP and ELISA.

Results

The combination of 4 guinea‐pig lipocalin allergens, including 2 new lipocalins, Cav p 1.0201 and Cav p 6.0101, and the previously characterized lipocalins Cav p 2 and Cav p 3, enabled the identification of 90% of all patients allergic to guinea‐pig. The vast majority had specific IgE to Cav p 1 (83%). Cav p 6 shares 54% sequence identity with Fel d 4 and Can f 6 and was found to be IgE‐cross‐reactive with these allergens. In the group of cat‐ and dog‐allergic patients, 73% had also specific IgE to guinea‐pig dander. However, only 27% of the cat /dog‐allergic patients had specific IgE to any of the non‐cross‐reactive guinea‐pig allergens Cav p 1, Cav p 2 or Cav p 3. The high prevalence of IgE to guinea‐pig dander could be explained by IgE‐cross‐reactivity among serum albumins and certain lipocalins.

Conclusions and clinical relevance

The availability of specific allergen markers is essential for the assessment of primary sensitization, especially in polysensitized patients. The proposed panel of guinea‐pig allergens Cav p 1, Cav p 2 and Cav p 3 is a first step to component‐resolved IgE‐diagnosis of allergy to small furry pets.
Central precocious puberty: Recent advances in understanding the aetiology and in the clinical approach
Authors: Maione Luigi , Bouvattier Claire , Kaiser Ursula B.
Published: April 2021

Central precocious puberty (CPP) results from early activation of the hypothalamic‐pituitary‐gonadal (HPG) axis. The current state of knowledge of the complex neural network acting at the level of the hypothalamus and the GnRH neuron to control puberty onset has expanded, particularly in the context of molecular interactions. Along with these advances, the knowledge of pubertal physiology and pathophysiology has also increased. This review focuses on regulatory abnormalities occurring at the hypothalamic level of the HPG axis to cause CPP. The clinical approach to diagnosis of puberty and pubertal disorders is also reviewed, with a particular focus on aetiologies of CPP. The recent identification of mutations in MKRN3 and DLK1 in familial as well sporadic forms of CPP has changed the state of the art of the approach to patients with CPP. Genetic advances have also had important repercussions beyond consideration of puberty alone. Syndromic disorders and central nervous system lesions associated with CPP are also discussed. If untreated, these conditions may lead to adverse physical, psychosocial and medical outcomes.
Serum vaspin levels and carotid intima‐media thickness in predialysis patients
Authors: Akyol Aytac , Demirkıran Davut , Akdag Serkan , Naci Aldemir Mehmet , Simsek Hakkı , Ali Gumrukcuoglu Hasan , Sahin Musa , Emre Habib
Published: April 2021

Background and Objective

Visceral adipose tissue‐derived serine proteinase inhibitor (vaspin) is an adipokine that correlates with insulin resistance and obesity in human beings. Previous studies have evaluated the serum vaspin levels in several diseases such as chronic haemodialysis patients and coronary artery disease. To our knowledge, serum vaspin levels have not yet been reported in predialysis patients. Carotid intima‐media thickness (CIMT) is a noninvasive procedure to detect early atherosclerotic changes. The aim of this study was to evaluate serum vaspin levels in predialysis patients and their relationships with glomerular filtration rate and CIMT levels.

Methods

A total of twenty‐five predialysis patients (14 females and 11 males) and 22 healthy subjects (8 females and 14 males) were enrolled in the study. Serum samples were subjected to the human vaspin RIA system. CIMT was measured by B‐mode ultrasonography.

Results

Serum vaspin levels were significantly lower in predialysis patients than control subjects (P < .05), while CIMT levels were significantly higher (P < .001). Serum vaspin levels were found to be significantly correlated with glomerular filtration rate (r = 0.42, P < .001) and CIMT (r = −0.47, P < .05) in predialysis patients.

Conclusions

This is the first report to describe the association between serum vaspin levels and CIMT in predialysis patients. We concluded that serum vaspin levels were decreased in predialysis patients than control subjects. In addition, serum vaspin levels were found to be significantly correlated with glomerular filtration rate and CIMT.
Characterization of benzodiazepine misuse and comorbidities in patients with alcohol use disorder
Authors: Lopez Elodie , Jeanne Guillaume , Lefort Laure‐Hélène , Autissier Cécile , Picot Marie‐Christine , Peyrière Hélène , Donnadieu‐Rigole Hélène
Published: April 2021

Background

Due to the frequent presence of anxious symptoms and sleep disorders, benzodiazepines (BZD) are often prescribed to patients with alcohol use disorder (AUD).

Objectives

To assess BZD misuse and psychiatric comorbidities in patients with AUD.

Methods

This prospective, monocentric study included all adult patients with AUD hospitalized in a French addiction unit for alcohol withdrawal from November 2017 to May 2018.

Results

Among the 153 patients included, 75 (49%) were using BZD at the time of their hospitalization. Duration of alcohol addiction was longer in BZD users: (33 ± 27 years vs. 29 ± 11 years; P = 0.001). BZD misuse was noted in 27 patients consuming benzodiazepines (36% of BZD users and 18% of all included patients), mainly increase in the dose (on average, 3 ± 4 times the prescribed dose). The most frequently misused benzodiazepines were diazepam (43.2%), alprazolam (18.9%), and lormetazepam (13.5%). The frequency of patients with lifetime use of cocaine or heroin was higher among BZD misusers than among non‐misusers (84.6% vs. 42.2%; <0.01 and 53.9% vs. 27.1%; P = 0.04). The frequency of patients consuming cocaine in the last month was higher in BZD misusers than in others: 16% versus 6%, P = 0.002. In multivariate analysis, age (OR=1.65 for 5 years, 95% CI = 1.19–2.27; P = 0.023), psychiatric comorbidities (at least one comorbidity: OR=6.03, 95% CI = 1.40–25.83; P = 0.015) and lifetime cocaine consumption (OR=4.37, 95% CI = 1.21–15.86; P = 0.025) were independently associated with BZD misuse.

Conclusion

BZD prescription for long periods might result in tolerance and dose increase. Educational therapy, prescribers’ awareness, and development of therapeutic alternatives are essential to limit BZD misuse.
Not So Dope: Marijuana Laws Should Include “Conduct Specific” Language to Prevent Unjustified Child Neglect Petitions Against Pot‐Smoking Parents
Authors: DeVivo Elizabeth Cecilia
Published: April 2021

The substance of marijuana is becoming legal in an increasing number of states. With the rise in legallity of marijuana comes a question of how will child protective agencies treat marijuana use by a parent or guardian. Family courts have continued to use the “actual harm” standard to determine child abuse and neglect. In addition to that standard, this Note proposes the adoption of “conduct specific” language into state marijuana statutes in order to further clarify for such agencies when investigations warrant a child neglect or abuse petition to be filed against parents.
Dispersants for silicon carbide in water—A comparative study
Authors: Foghmoes Søren , Jørgensen Jan Hoffmann , Agersted Karsten , Nielsen Marianne , Della Negra Michela
Published: April 2021

The present work describes a comparative study on a pool of 12 dispersants for the de‐agglomeration and stabilization of silicon carbide in aqueous suspensions with solids loading relevant for dip coating applications. As silicon carbide slurries may include sintering aids, different functional groups, molecular weight, and stabilization mechanisms were considered for the dispersants to be able to stabilize both slurry components. Additionally, pH effect, toxicity, additive compatibility, and foaming properties were considered, giving all the necessary information for developing new aqueous formulation of SiC suspensions, including advantages and disadvantages of the different candidates. Different de‐agglomeration procedures, powder surface area, and calcination temperature were also considered to study the effect of the SiC surface properties. The outcome is that slurry stabilization provided by an alkaline environment at pH larger than 8‒9 is significantly more effective than slurry stabilization by any of the tested dispersants. Alkaline environments facilitate a negative surface charge on SiC particles and provide a stable electrostatic stabilization mechanism not observed in neutral or acidic environments. One among the dispersant candidates (FA 4404) seems to broaden slightly the range of stability toward the acidic regime. Anionic surfactants or block co‐polymers tested exhibited no significant interaction with the SiC particles.
Exosomes from neuronal stem cells may protect the heart from ischaemia/reperfusion injury via JAK1/2 and gp130
Authors: Katsur Miroslava , He Zhenhe , Vinokur Vladimir , Corteling Randolph , Yellon Derek M , Davidson Sean M
Published: April 2021

Myocardial infarction requires urgent reperfusion to salvage viable heart tissue. However, reperfusion increases infarct size further by promoting mitochondrial damage in cardiomyocytes. Exosomes from a wide range of different cell sources have been shown to activate cardioprotective pathways in cardiomyocytes, thereby reducing infarct size. Yet, it is currently challenging to obtain highly pure exosomes in quantities enough for clinical studies. To overcome this problem, we used exosomes isolated from CTX0E03 neuronal stem cells, which are genetically stable, conditionally inducible and can be produced on an industrial scale. However, it is unknown whether exosomes from neuronal stem cells may reduce cardiac ischaemia/reperfusion injury. In this study, we demonstrate that exosomes from differentiating CTX0E03 cells can reduce infarct size in mice. In an in vitro assay, these exosomes delayed cardiomyocyte mitochondrial permeability transition pore opening, which is responsible for cardiomyocyte death after reperfusion. The mechanism of MPTP inhibition was via gp130 signalling and the downstream JAK/STAT pathway. Our results support previous findings that exosomes from non‐cardiomyocyte‐related cells produce exosomes capable of protecting cardiomyocytes from myocardial infarction. We anticipate our findings may encourage scientists to use exosomes obtained from reproducible clinical‐grade stocks of cells for their ischaemia/reperfusion studies.
Emission reduction strategies in the EU steel industry: Implications for business model innovation
Authors: Axelson Matilda , Oberthür Sebastian , Nilsson Lars J.
Published: April 2021

The European steel industry must achieve deep greenhouse gas emission reductions to become climate neutral by 2050. New business models are often proposed as one of the key solutions but are mostly addressed in general terms, without elaborating on or systematically analyzing how these new business models are actually linked to specific mitigation measures or strategies. In this paper, we assess when and to what extent different emission reduction strategies in the EU steel industry have implications for business model innovation. Through a review of 42 recent publications on industrial decarbonization, we identify 9 types of decarbonization strategies for steelmaking and their emission reduction potential. The strategies achieve emission reductions through material efficiency, emission efficiency, or a combination of both. For each strategy, we analyze the need for incremental or radical changes in business models on the basis of a thorough reading of the business model literature. Our findings show that EU steel firms can pursue several strategies to decarbonize without having to radically innovate their business models. Importantly, material efficiency strategies, arguably key to decarbonization, imply more radical changes to business models than emission efficiency strategies. Our study is a first contribution to the systematic assessment of industrial decarbonization strategies from a business model perspective. It is also an attempt to bring more rigor to the understanding of the role of business models in industrial decarbonization.
Imaging error compensation method for through‐focus scanning optical microscopy images based on deep learning
Authors: Qu Yufu , Ren Jiajun , Peng Renju , Wang Qianyi
Published: April 2021

Through‐focus scanning optical microscopy (TSOM) is a model‐based nanoscale metrology technique which combines conventional bright‐field microscopy and the relevant numerical simulations. A TSOM image is generated after through‐focus scanning and data processing. However, the mechanical vibration and optical noise introduced into the TSOM image during image generation can affect the measurement accuracy. To reduce this effect, this paper proposes a imaging error compensation method for the TSOM image based on deep learning with U‐Net. Here, the simulated TSOM image is regarded as the ground truth, and the U‐Net is trained using the experimental TSOM images by means of a supervised learning strategy. The experimental TSOM image is first encoded and then decoded with the U‐shaped structure of the U‐Net. The difference between the experimental and simulated TSOM images is minimised by iteratively updating the weights and bias factors of the network, to obtain the compensated TSOM image. The proposed method is applied for optimising the TSOM images for nanoscale linewidth estimation. The results demonstrate that the proposed method performs as expected and provides a significant enhancement in accuracy.
Digitomotography in children with oro‐facial dysfunction (OFD, oro‐facial myofunctional disorders) and childhood apraxia of speech (CAS)
Authors: Stahl Friederike , Pollex Dörte , Mathmann Philipp , Weinhold Leonie , Rohrbach Saskia
Published: April 2021

Background

Oro‐facial dysfunctions (OFDs; oro‐facial myofunctional disorders) in children and childhood apraxia of speech (CAS) often cause severe problems in articulation, chewing, swallowing and oral posture.

Objectives

Pathognomonic symptoms could yet not be identified, but central problems in planning, programming, timing and automating oro‐facial, as well as other fine motor skills, are assumed to be affected.

Methods

To investigate the nature of motor and coordinative deficits in OFD and CAS, digitomotography was applied. The testing focused on recording frequency, force, rhythm and regularity of the index finger including speeded and metronome tapping tasks. 25 children with OFD (7 girls and 18 boys, age 7.9 ± 2.3) and 5 children with CAS (0 girls and 5 boys, age 7.6 ± 2.3), and 31 healthy controls (12 girls and 19 boys, age 9.3 ± 2.2) were tested. Statistical significance was accepted at α = 0.05. ANOVA test, non‐parametric Mann‐Whitney U test, Kruskal‐Wallis test and Spearman's rank correlation coefficient were used.

Results

Cross‐sectional data revealed consistent significant differences between children with OFD and healthy controls concerning frequency, force, rhythm and regularity of index finger tapping. Individuals with CAS showed particularly low results. Tapping results correlated with disease burden.

Conclusion

These findings support that underlying superordinated sensorimotor deficits exist. This may help phenotyping and influence diagnostical and therapeutical approaches.
The impact of an undergraduate students' culture on their learning about mental health: A scoping review
Authors: Hansen Alison , McGarry Denise , Johnson Amanda , Roche Michael A.
Published: April 2021

Mental disorders are highly prevalent. This necessitates undergraduate students in health‐related courses are provided with the knowledge, skills, and attitudes to deliver safe care. Research confirms undergraduate health students maintain discriminative, stigmatizing, and inaccurate beliefs and attitudes toward those experiencing mental disorders. However, there is a paucity of research exploring how culture influences these beliefs. This scoping review addressed the question: ‘What is the impact of an undergraduate student's culture on their learning about mental health?’ A systematic search was undertaken of the MEDLINE, CINAHL, Scopus, PsycINFO, and ERIC databases. Results indicate variance between students' cultural beliefs in their attitudes toward and knowledge of mental disorders and understanding of interventions and treatment. None of the identified studies reviewed the ramifications for pedagogy beyond anecdotal suggestions. Educators need to acknowledge the potential impact that students' cultural beliefs have on their learning about mental health and consider appropriate learning activities to acknowledge the role of culture. Research of the impact of undergraduate students' culture on their learning about mental health will provide an evidence base for the development of these learning activities.
Mothers' habitual smartphone use, infants during breastfeeding, and mother–infant bonding: A longitudinal study
Authors: Inoue Chiaki , Hashimoto Yuri , Ohira Mitsuko
Published: April 2021

The excessive use of digital media by breastfeeding mothers may reduce their responsiveness to their child. However, there are no longitudinal studies focusing on breastfeeding during infancy. This study aimed to examine mothers' habitual use of smartphones and their observations of their infants during breastfeeding and identifies changes in the relationship between mother's breastfeeding habits and bonding with their infants. This is a quantitative descriptive study based on a questionnaire survey conducted on the Internet. Two questionnaires were sent to and collected from Japanese mothers who were the registered members of the survey company; the first questionnaire was completed 1 to 3 months postdelivery and the second 6 months after the first (approximately 9 months after delivery). In total, 195 participants participated. Smartphone use during breastfeeding was habitual, but mothers simultaneously observed their infants. Mothers habitually used smartphones during breastfeeding shortly after giving birth; however, there was little connection to subsequent negative emotions toward their children or problems with bonding. It is necessary to continue to evaluate the behavior of the mother and child.
Barriers and enablers of intensive care unit nurses' assessment and management of patients' pain
Authors: Hamdan Khaldoun M. , Shaheen Abeer M. , Abdalrahim Maysoon S.
Published: April 2021

Background

Inadequate pain assessment and management is a problem in hospitalized patients that impairs their well‐being. Intensive care unit nurses' pain practices are affected by several barriers and enablers.

Aims and objectives

To explore intensive care unit nurses' pain education, perceived barriers, and enablers of pain assessment and management practices among critically ill patients.

Design

A cross‐sectional descriptive design was used in the study.

Methods

Convenience sampling technique was used, including 300 nurses recruited from 22 intensive care units in Jordan. The Pain Assessment and Management for Critically Ill Adults Survey was used to collect data. Descriptive statistics, spearman correlation, and chi‐square tests were used to analyse the data.

Results

Only 127 (42.3%) of the nurses reported moderate to extreme satisfaction about receiving professional development education related to pain among critically ill patients. Nurse workload (65.3%), patient instability (54.4%), patient inability to communicate (53.3%), and sedation interfering with pain assessment (50%) were reported by nurses as the most frequent barriers impacting pain assessment and management. Enablers of pain assessment and management reported most frequently were “pain assessment and management is a unit priority” (63.7%), “enthusiastic and motivated staff” (61.3%), “protocols and guidelines are in use” (57.4%), and “standardized assessment tools are in use” (57%). Some barriers and enablers to pain assessment and management and pain education differed significantly according to nurses' experience and hospital type.

Conclusion

This study identified a range of enablers and barriers to pain assessment and management practices perceived by intensive care unit nurses. Nurse workload was an important barrier while making pain assessments, and management a unit priority was an important enabler for pain assessment and management. Frequent assessment of barriers and enablers of pain assessment and management is needed in critical care units to improve nurses' practices. Pain education should be included in the hospitals' continuous educational program.
Mass spectrometry‐based quantification and spatial localization of small organic acid exudates in plant roots under phosphorus deficiency and aluminum toxicity
Authors: Gomez‐Zepeda David , Frausto Moises , Nájera‐González Héctor‐Rogelio , Herrera‐Estrella Luis , Ordaz‐Ortiz José‐Juan
Published: April 2021

Low‐molecular‐weight organic acid (OA) extrusion by plant roots is critical for plant nutrition, tolerance to cations toxicity, and plant–microbe interactions. Therefore, methodologies for the rapid and precise quantification of OAs are necessary to be incorporated in the analysis of roots and their exudates. The spatial location of root exudates is also important to understand the molecular mechanisms directing OA production and release into the rhizosphere. Here, we report the development of two complementary methodologies for OA determination, which were employed to evaluate the effect of inorganic ortho‐phosphate (Pi) deficiency and aluminum toxicity on OA excretion by Arabidopsis roots. OA exudation by roots is considered a core response to different types of abiotic stress and for the interaction of roots with soil microbes, and for decades has been a target trait to produce plant varieties with increased capacities of Pi uptake and Al tolerance. Using targeted ultra‐performance liquid chromatography coupled with high‐resolution tandem mass spectrometry (UPLC‐HRMS/MS), we achieved the quantification of six OAs in root exudates at sub‐micromolar detection limits with an analysis time of less than 5 min per sample. We also employed targeted (MS/MS) matrix‐assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) to detect the spatial location of citric and malic acid with high specificity in roots and exudates. Using these methods, we studied OA exudation in response to Al toxicity and Pi deficiency in Arabidopsis seedlings overexpressing genes involved in OA excretion. Finally, we show the transferability of the MALDI‐MSI method by analyzing OA excretion in Marchantia polymorpha gemmalings subjected to Pi deficiency.