bluuebunny/crossref_metadata_2025 huggingface dataset:
SARS-CoV-2 transmission chains from genetic data: a Danish case study
Authors: Bluhm Andreas , Christandl Matthias , Gesmundo Fulvio , Klausen Frederik Ravn , Mančinska Laura , Steffan Vincent , França Daniel Stilck , Werner Albert H.
Published: May 2020

Background

The COVID-19 pandemic caused by the SARS-CoV-2 virus started in China in December 2019 and has since spread globally. Information about the spread of the virus in a country can inform the gradual reopening of a country and help to avoid a second wave of infections. Denmark is currently opening up after a lockdown in mid-March.

Methods

We perform a phylogenetic analysis of 742 publicly available Danish SARS-CoV-2 genome sequences and put them into context using sequences from other countries.

Result

Our findings are consistent with several introductions of the virus to Denmark from independent sources. We identify several chains of mutations that occurred in Denmark and in at least one case find evidence that the virus spread from Denmark to other countries. A number of the mutations found in Denmark are non-synonymous, and in general there is a considerable variety of strains. The proportions of the most common haplotypes is stable after lockdown.

Conclusion

Our work shows how genetic data can be used to identify routes of introduction of a virus into a region and provide alternative means for verifying existing assumptions. For example, our analysis supports the hypothesis that the virus was brought to Denmark by skiers returning from Ischgl. On the other hand, we identify transmission chains suggesting that Denmark was part of a network of countries among which the virus was being transmitted; thus challenging the common narrative that Denmark only got infected from abroad. Our analysis does not indicate that the major haplotypes appearing in Denmark have a different degree of virality. Our methods can be applied to other countries, regions or even highly localised outbreaks. When used in real-time, we believe they can serve to identify transmission events and supplement traditional methods such as contact tracing.
TowardsMycobacterium tuberculosisdetection at the point-of-care: a brighter solvatochromic probe permits the detection of mycobacteria within minutes
Authors: Kamariza Mireille , Keyser Samantha G. L. , Utz Ashley , Knapp Benjamin D. , Ahn Green , Cambier C. J. , Chen Teresia , Huang Kerwyn Casey , Bertozzi Carolyn R.
Published: May 2020

There is an urgent need for point-of-care tuberculosis (TB) diagnostic methods that are fast, inexpensive, and operationally simple. Here, we report on a bright solvatochromic dye trehalose conjugate that specifically detectsMycobacterium tuberculosis(Mtb) in minutes. 3-hydroxychromone (3HC) dyes, known to yield high fluorescence quantum yields, exhibit shifts in fluorescence intensity in response to changes in environmental polarity. We synthesized two analogs of 3HC-trehalose conjugates (3HC-2-Tre and 3HC-3-Tre) and determined that 3HC-3-Tre has exceptionally favorable properties for Mtb detection. 3HC-3-Tre-labeled mycobacterial cells displayed a 10-fold increase in fluorescence intensity compared to our previously reports on the dye 4,4-N,N-dimethylaminonapthalimide (DMN-Tre). Excitingly, we detected fluorescent Mtb cells within 10 minutes of probe treatment. Thus, 3HC-3-Tre permits rapid visualization of mycobacteria that ultimately could empower improved Mtb detection at the point-of-care in low-resource settings.
GeneBreaker - Variant simulation to improve the diagnosis of Mendelian rare genetic diseases
Authors: Richmond Phillip A. , Av-Shalom Tamar V. , Fornes Oriol , Modi Bhavi , Elliott Alison M. , Wasserman Wyeth W.
Published: May 2020

Mendelian rare genetic diseases affect 5-10% of the population, and with over 5,300 genes responsible for ~7,000 different diseases, they are challenging to diagnose. The use of whole genome sequencing (WGS) has bolstered the diagnosis rate significantly. Effective use of WGS relies upon the ability to identify the disrupted gene responsible for disease phenotypes. This process involves genomic variant calling and prioritization, and is the beneficiary of improvements to sequencing technology, variant calling approaches, and increased capacity to prioritize genomic variants with potential pathogenicity. As analysis pipelines continue to improve, careful testing of their efficacy is paramount. However, real-life cases typically emerge anecdotally, and utilization of clinically sensitive and identifiable data for testing pipeline improvements is regulated and limiting. We identified the need for a gene-based variant simulation framework which can create mock rare disease scenarios, utilizing known pathogenic variants or through the creation of novel gene-disrupting variants. To fill this need, we present GeneBreaker, a tool which creates synthetic rare disease cases with utility for benchmarking variant calling approaches, testing the efficacy of variant prioritization, and as an educational mechanism for training diagnostic practitioners in the expanding field of genomic medicine. GeneBreaker is freely available athttp://GeneBreaker.cmmt.ubc.ca.
A simple Stochastic model for the SARS-CoV-2 Epidemic curve
Authors: Diogenes Alysson Nunes , Tedesco Daniel Guimaraes
Published: May 2020

An epidemic curve is a graphic depiction of the number of outbreak cases by date of illness onset, ordinarily constructed after the disease outbreak is over. However, a good estimate of the epidemic curve early in an outbreak would be invaluable to health care officials. On the other hand, from the end of February, the SARS-CoV-2 epidemic in Brazil seems to not follow the Europe, or in particular, Italy or Spain. Even if less tests have been applied, there are less deaths occurring in Brazil than in both cited countries. However, since few tests were applied, there is no certain planning on the real number of active cases. To estimate the number of future cases, epidemiologists make an educated guess as to how many people might become affected. We have proposed a simple fitting model using a simulated annealing technique, testing it with the South Korea data. We have tested and discussed the uncertainties of the model. We also have analyzed the trends in the confirmed cases using this model for the five most affected countries plus Brazil along several epidemic weeks.
Objective dystonia prediction with MRI after neonatal hypoxic-ischemic encephalopathy
Authors: Chintalapati Keerthana , Miao Hanyang , Mathur Amit , Neil Jeff , Aravamuthan Bhooma R.
Published: May 2020

Aim

To determine an objective and clinically-feasible method to predict dystonia in cerebral palsy (CP) using magnetic resonance imaging (MRI) following neonatal hypoxic-ischemic encephalopathy (HIE).

Methods

In this retrospective case-control study, we examined brain MRIs in neonates at age 4–5 days who underwent therapeutic hypothermia for HIE at a single tertiary care center. The lower average apparent diffusion coefficient (ADC) values between the left and right striatum and thalamus were determined using clinically-integrated software (IBM iConnect Access). Neonatal neurology, movement disorder, and cerebral palsy specialist notes were screened through age 5 years for motor abnormality documentation.

Results

In 50 subjects, ADC values significantly predicted dystonia in CP with receiver operator characteristic areas under the curve of 0.862 (p = 0.0004) in the striatum and 0.838 (p = 0.001) in the thalamus. Striatal ADC values less than 1.014×10−3 mm2/s provided 100% specificity and 70% sensitivity for dystonia. Thalamic ADC values less than 0.973×10−3 mm2/s provided 100% specificity and 80% sensitivity for dystonia.

Interpretation

In this small retrospective study, analysis of clinically-acquired MRIs predicted dystonia with high specificity following neonatal HIE. This could be a useful prognostication adjunct guiding when to establish appropriate vigilance for dystonia in CP.
Predicting Growth of COVID-19 Confirmed Cases in Each U.S. County with a Population of 50,000 or More, Revised July 8, 2020
Authors: Robertson Leon S.
Published: May 2020

A simple model of local spread of COVID-19 is needed to assist local governments and health care providers prepare for surges of clinical cases in their communities. National and state based models are inadequate because the virus is introduced and spreads at different rates in local areas. In the U.S. as of July 3, 2020, 73 percent of cases and 84 percent of deaths occurred in the 200 counties with the most cases and deaths. Each county has its own function of cases in time that can be used to predict increases in reported cases two weeks in advance for each of 988 counties in the U.S. with populations of 50,000 or more inhabitants. A logarithmic model based on growth in cases during the past 30 days is substantially predictive of increase in cases during the subsequent 14 days. Predicted increase in cases for the 988 U.S. counties will be published online daily.
Financial reporting quality, audit fees and risk committees
Authors: Bhuiyan Md. Borhan Uddin , Salma Ummya , Roudaki Jamal , Tavite Siata
Published: May 2020

Purpose

The purpose of this paper is to examine the association between the existence of a risk committee (RC) in a firm and financial reporting quality. We also investigate whether having an RC has an effect on audit pricing. We argue that the existence of an RC in a firm contributes to higher financial reporting quality and this, eventually, affects audit pricing.

Design/methodology/approach

This study uses two different proxies for RC measures and investigates the impact on financial reporting quality and audit pricing. Multivariate regression analysis and propensity score matching techniques are both applied to data from the Australian Stock Exchange's listed companies for the years 2001–2013.

Findings

The results indicate that the existence of an RC reduces the discretionary accruals; this means the financial reporting quality improves when RCs are in operation. Our findings also indicate that the existence of an RC increases audit fees.

Practical implications

The findings from this study will be beneficial to the regulatory authorities responsible for improving the compliance of corporate governance (CG). An RC can serve as a risk-mitigating tool in the investment decision-making process. Finally, the results are beneficial for the development of best practices in CG by promoting the existence of an RC.

Originality/value

This study goes beyond the traditional focus on CG as we use the existence of an RC as an indicator of better governance practices to mitigate financial and non-financial risk factors. To the best of our knowledge, this paper is among the first to investigate the consequences for firms operating with RCs. This issue has implications for investors, auditors, directors and regulators.
Inefficacy: the tipping point of driver burnout
Authors: Thomas Stephanie P. , Liao-Troth Sara , Williams Donnie F.
Published: May 2020

Purpose

Truck drivers keep supply chains moving, but driver shortages and high turnover levels plague the industry. The purpose of this research is to examine the three dimensions of Maslach's job burnout model: exhaustion, cynicism and professional inefficacy, as it relates to role stressors and turnover intention. Logistics boundary spanners such as truck drivers appear to be especially susceptible to job burnout. Role theory and organizational support theory were used to develop hypotheses.

Design/methodology/approach

Individual level survey data were collected from 190 truck driver respondents (not owner operators) at two large truck stops. Data were analyzed using structural equation modeling.

Findings

Findings suggest that the relationship between role stressors and the dimensions of job burnout are not all the same. Role conflict significantly impacts exhaustion and cynicism. Role ambiguity significantly impacts cynicism and inefficacy. Results support a progression through burnout dimensions that begins with exhaustion and ends with inefficacy. Inefficacy was significantly related to intention to stay. Organizational support is a way to help drivers mitigate feelings of inefficacy.

Practical implications

Managers in trucking organizations can track burnout levels in their drivers using the Maslach Burnout Inventory with a specific focus on monitoring feelings of inefficacy, which may help lower turnover levels.

Originality/value

The findings support that the burnout dimension of inefficacy is the strongest indicator that a driver is considering leaving his current organization or the industry. This is contrary to other studies that have focused on the other two burnout dimensions.
A meaning-based framework for customer loyalty
Authors: Närvänen Elina , Kuusela Hannu , Paavola Heli , Sirola Noora
Published: May 2020

Purpose

This paper's purpose is to develop a meaning-based framework for customer loyalty by examining how consumers make sense of customer loyalty through meanings and metaphors.

Design/methodology/approach

A qualitative study based on in-depth interviews and focus group data in the retail context was conducted with Finnish customers. The data were analysed with qualitative data analysis techniques such as the constant comparative technique.

Findings

The empirical findings comprise eight loyalty meanings characterised by two dimensions. The first dimension is reflexive vs. routinised, and the second dimension is private vs. social. The loyalty types are dimensionalised through four metaphors: loyalty as freedom of choice; as being conventional and binding; and as belongingness.

Practical implications

The findings improve the way customer loyalty currently is understood in the retail setting. The paper proposes that customer insight that utilises thick data can be used to grasp loyalty meanings. These data are rich in context and detail, and they take into account customers' everyday lives. Utilising thick data in the form of storytelling fuels customers' meaning-making related to customer loyalty, potentially enriching their relationship with the retailer.

Originality/value

Customer loyalty has been driven largely by a transactional and company-centric perspective. This article presents an alternative view of customer loyalty that accounts for the variety of meanings that customers may assign to their loyalty-related thoughts and behaviours.
Expatriate management in hostile environments from a multi-stakeholder perspective – a systematic review
Authors: Faeth Pia Charlotte , Kittler Markus G.
Published: May 2020

Purpose

The successful management of business expatriates and their families in hostile environments (HE) is a current concern for academics and human resources (HR) practitioners alike. Terrorism and other forms of violent crime have become salient topics on the public agenda, and international organizations are increasingly affected. Hence, scholarly interest in the HR implications for organizations sending staff to HEs has recently grown, and a nascent research area has emerged. This paper is the first systematic review synthesizing emerging literature in the field of expatriate management in HEs and its theoretical foundations, applying a multi-stakeholder perspective.

Design/methodology/approach

Following accepted review procedures, systematic searches were conducted across three major databases. Manual search in target journals provided additional scrutiny.

Findings

After analysing 28 articles, four main stakeholders were identified as follows: environments, expatriates, assigning organizations and the expatriates' social networks. Findings reveal the ways of how all stakeholders can affect expatiation success or be affected so that the success of the assignment is jeopardised.

Originality/value

Our paper illustrates how these diverse articles can be linked within a comprehensive multi-stakeholder framework and provides avenues for future research. We also shift attention to neglected theoretical perspectives that might further improve the understanding of expatriates in HEs while offering actionable guidance for managerial and organizational practices.
Rock‐physics forward modelling to predict seismic behaviour: A case study for exploration target in Mahanadi basin, East Coast of India
Authors: Mondal Samit , Yadav Ashok , Chatterjee Rima
Published: May 2020

One of the major aspects of rock‐physics forward modelling is to predict seismic behaviour at an undrilled location using drilled well data. It is important to model the rock and fluid properties away from drilled wells to characterize the reservoir and investigate the root causes of different seismic responses. Using the forward modelling technique, it is possible to explain the amplitude responses of present seismic data in terms of probable rock and reservoir properties. In this context, rock‐physics modelling adds significant values in the prospect maturation process by reducing the risk of reservoir presence in exploration and appraisal phases. The synthetic amplitude variation with offset gathers from the forward model is compared with real seismic gathers to ensure the fidelity of the existing geological model. ‘Prospect A’ in the study area has been identified from seismic interpretation, which was deposited as slope fan sediments in Mahanadi basin, East Coast of India. The mapped prospect has shown class‐I amplitude variation with offset response in seismic without any direct hydrocarbon indicator support. The existing geological model suggests the presence of an excellent gas reservoir with proven charge access from the fetch area, moderate porosity and type of lithology within this fan prospect. But, whether the seismic response from this geological model will exhibit a class‐I amplitude variation with offset behaviour or ‘dim spot’ will be visible; the objective of the present study is to investigate these queries. A rock‐physics depth trend analysis has been done to envisage the possibilities of class‐I reservoir in ‘Prospect A’. Forward modelling, using a combination of mechanical and chemical compaction, shows the synthetic gas gathers at ‘Prospect A’, which are class I in nature. The study has also depicted 2D forward modelling using lithology and fluid properties of discovery well within similar stratigraphy to predict whether ‘dim spot’ will be seen in seismic. The estimated change in synthetic amplitude response has been observed as ∼5% at contact, which suggests that the changes will not be visible in seismic. The study connects the existing geological model with a top‐down seismic interpretation using rock‐physics forward modelling technique to mature a deep‐water exploratory prospect.
assignR: An r package for isotope‐based geographic assignment
Authors: Ma Chao , Vander Zanden Hannah B. , Wunder Michael B. , Bowen Gabriel J.
Published: May 2020

Methods for inferring geographic origin from the stable isotope composition of animal tissues are widely used in movement ecology, but few computational tools and standards for data interpretation are available.

We introduce the assignR r package, which provides a structured, flexible toolkit for isotope‐based migration data analysis and interpretation using a widely adopted semi‐parametric Bayesian inversion method.

assignR bundles data resources and functions that support data interpretation, hypothesis‐testing and quality assessment, allowing end‐to‐end data analysis with only a few lines of code. Tools for post hoc analysis offer robust, standardized methods for aggregating information from multiple individuals, assignment of individuals to a sub‐region of the study area and comparison of potential regions of origin using odds ratios. Assessment tools quantify the quality and power of the isotopic assignments and can be used to test prototype study designs.

The assignR package should increase the accessibility of isotopic geolocation methods. assignR supports flexible data sources and analysis decisions, making it suitable for a wide range of applications, but also promotes standardization that will help foster increased consistency and comparability among studies and a more holistic understanding of animal migration. Lastly, assignR can help make isotope‐based geolocation research more efficient by helping researchers plan projects to be optimally aligned with their research questions.
Nutritional Deficits In Children With Cancer: A Situation‐Specific Theory
Authors: Teixeira Iane Ximenes , de Oliveira Lopes Marcos Venícios , Diniz Camila Maciel
Published: May 2020

PURPOSE

To construct a situation‐specific theory (SST) to represent nutritional deficits for assessing children with cancer.

DATA SOURCES

Literature review.

DATA SYNTHESIS

The SST included the definition of key concepts, a pictorial scheme, propositions, causal relationships, and evidence for nursing practice.

CONCLUSIONS

It was possible to characterize the elements as antecedent and consequent clinical factors to allow for an understanding of the existing relationships between them and their temporality. These elements differed considerably from those included in NANDA International.

IMPLICATIONS FOR NURSING PRACTICE

This study provides additional information so that nurses in clinical practice can infer the presence of nutritional deficits in children with cancer early, given the risk already inherent in the diagnosis of cancer and treatment.
Acute Alcohol Intake Produces Widespread Decreases in Cortical Resting Signal Variability in Healthy Social Drinkers
Authors: Sevel Landrew , Stennett Bethany , Schneider Victor , Bush Nicholas , Nixon Sara Jo , Robinson Michael , Boissoneault Jeff
Published: May 2020

Background

Acute alcohol intoxication has wide‐ranging neurobehavioral effects on psychomotor, attentional, inhibitory, and memory‐related cognitive processes. These effects are mirrored in disruption of neural metabolism, functional activation, and functional network coherence. Metrics of intraregional neural dynamics such as regional signal variability (RSV) and brain entropy (BEN) may capture unique aspects of neural functional capacity in healthy and clinical populations; however, alcohol’s influence on these metrics is unclear. The present study aimed to elucidate the influence of acute alcohol intoxication on RSV and to clarify these effects with subsequent BEN analyses.

Methods

26 healthy adults between 25 and 45 years of age (65.4% women) participated in 2 counterbalanced sessions. In one, participants consumed a beverage containing alcohol sufficient to produce a breath alcohol concentration of 0.08 g/dl. In the other, they consumed a placebo beverage. Approximately 35 minutes after beverage consumption, participants completed a 9‐minute resting‐state fMRI scan. Whole‐brain, voxel‐wise standard deviation was used to assess RSV, which was compared between sessions. Within clusters displaying alterations in RSV, sample entropy was calculated to assess BEN.

Results

Compared to the placebo, alcohol intake resulted in widespread reductions in RSV in the bilateral middle frontal, right inferior frontal, right superior frontal, bilateral posterior cingulate, bilateral middle temporal, right supramarginal gyri, and bilateral inferior parietal lobule. Within these clusters, significant reductions in BEN were found in the bilateral middle frontal and right superior frontal gyri. No effects were noted in subcortical or cerebellar areas.

Conclusions

Findings indicate that alcohol intake produces diffuse reductions in RSV among structures associated with attentional processes. Within these structures, signal complexity was also reduced in a subset of frontal regions. Neurobehavioral effects of acute alcohol consumption may be partially driven by disruption of intraregional neural dynamics among regions involved in higher‐order cognitive and attentional processes.
Ethanol and Cannabinoids Regulate Zebrafish GABAergic Neuron Development and Behavior in a Sonic Hedgehog and Fibroblast Growth Factor‐Dependent Mechanism
Authors: Boa‐Amponsem Oswald , Zhang Chengjin , Burton Derek , Williams Kevin P. , Cole Gregory J.
Published: May 2020

Background

Ethanol (EtOH) has diverse effects on nervous system development, which includes development and survival of GABAergic neurons in a sonic hedgehog (Shh) and fibroblast growth factor (Fgf)‐dependent mechanism. Cannabinoids also function as inhibitors of Shh signaling, raising the possibility that EtOH and cannabinoids may interact to broadly disrupt neuronal function during brain development.

Methods

Zebrafish embryos were exposed to a range of EtOH and/or cannabinoid receptor 1 (CB1R) agonist concentrations at specific developmental stages, in the absence or presence of morpholino oligonucleotides that disrupt shh expression. In situ hybridization was employed to analyze glutamic acid decarboxylase (gad1) gene expression as a marker of GABAergic neuron differentiation, and zebrafish behavior was analyzed using the novel tank diving test as a measure of risk‐taking behavior.

Results

Combined acute subthreshold EtOH and CB1R agonist exposure results in a marked reduction in gad1 mRNA expression in zebrafish forebrain. Consistent with the EtOH and cannabinoid effects on Shh signaling, fgf8 mRNA overexpression rescues the EtOH‐ and cannabinoid‐induced decrease in gad1 gene expression and also prevents the changes in behavior induced by EtOH and cannabinoids.

Conclusions

These studies provide evidence that forebrain GABAergic neuron development and zebrafish risk‐taking behavior are sensitive to both EtOH and cannabinoid exposure in a Shh‐ and Fgf‐dependent mechanism, and provide additional evidence that a signaling pathway involving Shh and Fgf crosstalk is a critical target of EtOH and cannabinoids in FASD.
It is currently unknown whether SARS‐CoV‐2 is viable in semen or whether COVID‐19 damages spermatozoa
Authors: Perry Melissa J. , Arrington Suzanne , Neumann Laura M. , Carrell Douglas , Mores Christopher N.
Published: May 2020

Research is needed to understand the presence of the SARS‐CoV‐2 virus in semen, sexual transmissibility, and impact on sperm quality. Several studies have examined men recovering from COVID‐19, but large‐scale community‐based testing is needed to ascertain the effects on the male reproductive tract, and the potential for prolonged transmission.
Visual‐motor functions are affected in young adults who were born premature and screened for retinopathy of prematurity
Authors: Pétursdóttir Dýrleif , Holmström Gerd , Larsson Eva , Böhm Birgitta
Published: May 2020

Aim

To assess visual‐motor integration in young adults previously included in a prospective study on the incidence of retinopathy of prematurity (ROP).

Methods

The study encompassed 59 preterm individuals, born 1988‐1990, with a birth weight ≤1500 g, and 44 full‐term controls, aged 25‐29 years. Ophthalmological examination, including visual acuity and contrast sensitivity, and the Beery Visual‐Motor Integration (VMI) with supplemental tests of visual perception and motor coordination, were performed. A short questionnaire was filled in.

Results

The preterm individuals had significantly lower scores than the controls in all VMI tests, median values and interquartile ranges: Beery VMI 87 (21) vs 103 (11), visual perception 97 (15) vs 101 (8) and motor coordination 97 (21) vs 102 (15), respectively. Within the preterm group, no correlations were found between the VMI tests and ROP, gestational age, birth weight or visual acuity. Contrast sensitivity was correlated to visual perception. Neurological complication at 2.5 years was a risk factor for lower scores on Beery VMI. The preterm subjects reported six times as many health problems as compared to the controls.

Conclusion

Being born preterm seemed to have life‐long effects. This study shows that visual‐motor integration was affected in young adults born preterm.
Compositional characterization of Etruscan earthen architecture and ceramic production
Authors: Ceccarelli L. , Moletti C. , Bellotto M. , Dotelli G. , Stoddart S.
Published: May 2020

This study presents the results of new research into Etruscan technology for earthen architecture as well as ceramic production in the upper Tiber Valley in central Italy, using as a case study the Etruscan settlement of Col di Marzo (Perugia). It determines the compositional differences of the raw material employed as building material and for ceramic production by X‐ray powder diffraction (XRD), thermogravimetric analysis and differential thermal analysis (TG‐DTG), Fourier‐transform infrared analysis (FTIR) and geotechnical analyses. The research also advances the knowledge of ceramic manufacturing technology, with a focus on impasto production, at Col di Marzo between the fifth and mid‐third centuriesbceand the surrounding territory on the left bank of the River Tiber. The compositional analysis of building material compared with the ceramics provides answers to questions related to their sourcing and deepens the understanding of the exploitation of natural resources.
Pacing emotional labour of qualitative research in an intractable conflict environment
Authors: Bundhoo Dilshaad , Lynch Kenneth
Published: May 2020

Qualitative field research in any type of terrain calls for a practice‐oriented reflection on the researcher's emotional labour management in relation to the context of the field before, during, and beyond data collection. Intractable conflict environments (ICE) are characterised by long‐running social crises still unresolved. This particularity makes such contexts risk‐prone in terms of unpredictable dangers and unexpected outcomes, hence, the requirement for thorough ethical evaluation of field research designs. Field researchers, often working on their own, are expected to safely make ethically sound decisions while gathering high‐quality data within complex social realities of which they are often socio‐culturally not savvy. This inevitably exacerbates the emotional burden on the researchers and makes fieldwork challenging. Although feminist geographers notably have significantly contributed to highlighting the social dynamics of fieldwork by initiating and deepening discussions of the emotional and ethical challenge, discussions have rarely gone beyond underlining the need for recognition of the field researchers' emotional labour. Despite academic consensus for reflexive analysis and field diary‐keeping, little has been discussed on how to systematically manage this effort during the research process. In this paper, building on the first author's PhD fieldwork experience in Israel and the West Bank area, we propose a paced field research organisation method – PFROM – which systematically accommodates time and space for the researcher's engagement with and detachment from the field research's intensity. Applying the concept of pacing – intentionally distributing focused attention in such a way that will reduce fatigue prior to the completion of a task – this framework systematically integrates reflexivity within research designs. The PFROM provides researchers with a tool applicable beyond intractable conflict contexts which has the potential to enhance their emotional labour management.
Opportunities for changes in the drug product design to enhance medication safety in older people: Evaluation of a national public portal for medication incidents
Authors: Karapinar‐Çarkit Fatma , van den Bemt Patricia M.L.A. , Sadik Mariam , van Soest Brigit , Knol Wilma , van Hunsel Florence , van Riet‐Nales Diana A.
Published: May 2020

Aims

Medication safety requires urgent attention in hospital pharmacy. This study evaluated the medication‐related problems/errors as reported to the Dutch medication incident registry and disseminated for information to pharmacists. Through analysis by an expert panel we aimed to better understand which problems could have been mitigated by the drug product design. Additionally, the (wider) implications of the problems for current hospital/clinical practice were discussed.

Methods

Items were extracted from the public Portal for Patient Safety. Items were included if relevant for older people and connected with the drug product design and excluded if they should reasonably have been intercepted by compliance to routine controls or well‐known professional standards in pharmaceutical care. To explore any underreporting of well‐known incidents, it was investigated if different medication‐related problems could be observed in a regional hospital practise over a 1‐month period. For 6 included items (cases), the implications for hospital/clinical practise were discussed in an expert panel.

Results

In total, 307 items were identified in the Portal for Patient Safety; all but 14 were excluded. Six cases were added from daily hospital practice. These 20 cases commonly related to confusing product characteristics, packaging issues such as the lack of a single unit package for an oncolytic product, or incorrect or incomplete user instructions.

Conclusion

Medication registries provide important opportunities to evaluate real‐world medication‐related problems. However, underreporting of well‐known problems should be considered. The product design can be used as an (additional) risk mitigation measure to support medication safety in hospital practice.
Potential dual functional roles of the Y‐linked RBMY in hepatocarcinogenesis
Authors: Kido Tatsuo , Tabatabai Z. Laura , Chen Xin , Lau Yun‐Fai Chris
Published: May 2020

Hepatocellular carcinoma (HCC) is a highly heterogeneous liver cancer with significant male biases in incidence, disease progression, and outcomes. Previous studies have suggested that genes on the Y chromosome could be expressed and exert various male‐specific functions in the oncogenic processes. In particular, the RNA‐binding motif on the Y chromosome (RBMY) gene is frequently activated in HCC and postulated to promote hepatic oncogenesis in patients and animal models. In the present study, immunohistochemical analyses of HCC specimens and data mining of The Cancer Genome Atlas (TCGA) database revealed that high‐level RBMY expression is associated with poor prognosis and survival of the patients, suggesting that RBMY could possess oncogenic properties in HCC. To examine the immediate effect(s) of the RBMY overexpression in liver cancer cells, cell proliferation was analyzed on HuH‐7 and HepG2 cells. The results unexpectedly showed that RBMY overexpression inhibited cell proliferation in both cell lines as its immediate effect, which led to vast cell death in HuH‐7 cells. Transcriptome analysis showed that genes involved in various cell proliferative pathways, such as the RAS/RAF/MAP and PIP3/AKT signaling pathways, were downregulated by RBMY overexpression in HuH‐7 cells. Furthermore, in vivo analyses in a mouse liver cancer model using hydrodynamic tail vein injection of constitutively active AKT and RAS oncogenes showed that RBMY abolished HCC development. These findings support the notion that Y‐linked RBMY could serve dual tumor‐suppressing and tumor‐promoting functions, depending on the spatiotemporal and magnitude of its expression during oncogenic processes, thereby contributing to sexual dimorphisms in liver cancer.
Biological evaluation of Keggin‐type polyoxometalates on tyrosinase: Kinetics and molecular modeling
Authors: Chi Guoxiang , Xie Lefang , Zhao Meijuan , Wang Li , Wang Fang , Li Jian , Zheng Aping
Published: May 2020

Abnormal overexpression of tyrosinase activity can lead to the production of hyperpigmentation in human skin and enzymatic browning in fruits and vegetables. Herein, the inhibition and mechanism of the H3PMo12O40 and two transition metal‐substituted Keggin‐type polyoxometalates (Na7PMo11CoO40 and Na7PMo11ZnO40) on tyrosinase were studied by kinetics and molecular modeling. Kinetic studies indicated that all compounds had more potent inhibitory activities than standard arbutin, and H3PMo12O40 (IC50 = 0.443 ± 0.006 mm) is ~15‐fold stronger inhibition than arbutin. Additionally, all compounds inhibited tyrosinase in a reversible competitive manner. Intriguingly, molecular modeling elucidated that three compounds competitively bind to tyrosinase mainly through more interactions with Cu2+ ions and the amino acid residue capable of forming cation‐π and hydrogen bonding, forming a reversible non‐covalent complex. Molecular simulation study correlated well with the biological activity of three compounds in vitro. This work provided new insights into design and synthesis of polyoxometalates as tyrosinase inhibitors in the field of medicine, cosmetic, and food.
MECP2 mutation spectrum and its clinical characteristics in a Chinese cohort
Authors: Wen Yongxin , Wang Jiaping , Zhang Qingping , Chen Yan , Wu Xiru , Bao Xinhua
Published: May 2020

The dysfunction of methyl‐CpG‐binding protein 2 (MeCP2) is associated with several neurological disorders, of which Rett syndrome (RTT) is the most prominent. This study focused on a Chinese patient cohort with MECP2 mutations, and analyzed the characteristics of these mutations and their clinical manifestations. In total, 666 patients were identified with 126 different MECP2 mutations, including 22 novel mutations. Over 80% of patients carried an MECP2 mutation on exon 4. Nonsense and missense mutations were the most commonly reported types. Missense mutations were mainly located on methyl‐CpG‐binding domain (MBD), and nonsense mutations predominantly occurred on transcription repression domain (TRD) and inter domain. The predilection site of large deletion was exon 3 and/or exon 4. Patients with p.R133C, p.R294*, p.R306C, and C‐terminal domain (CTD) deletions were less severely affected. Significant differences were found in ambulation ability, hand function, and language among different mutation groups. Three female patients with MECP2 mutations (1 with p.R306P and 2 with p.R309W) only presented with intellectual disability/developmental delay (ID/DD), and no obvious RTT symptoms were reported. Eight male individuals with MECP2 mutations were also identified in this study, including 2 diagnosed with typical RTT, 3 with atypical RTT and 3 with ID/DD.
Troubleshooting for severe acute cholangitis caused by proximally migrated metal stent into the intrahepatic bile duct: Stent shortening via a balloon catheter
Authors: Yamakawa Kohei , Masuda Atsuhiro , Kodama Yuzo
Published: May 2020

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Tricuspid valve geometry in patients with functional tricuspid regurgitation: A three‐dimensional echocardiographic study
Authors: Karamali Fatemeh , Hosseini Saeid , Shojaeifard Maryam , Mohammadi Khadijeh , Kaviani Raheleh , Rezaei Yousef , Samiei Niloufar
Published: May 2020

Introduction

Tricuspid valve (TV) has a complex anatomy causing some difficulties in echocardiographic evaluation. In this study, we sought to assess the geometry of TV in patients with functional tricuspid regurgitation (TR) by the implementation of 2‐ and 3‐dimennsional (2D and 3D) echocardiography.

Methods

In a case–control study, the geometrical features of TV were evaluated in forty patients with functional TR using echocardiographic examinations, and those data compared with twenty‐five age‐ and sex‐matched healthy individuals.

Results

The mean age of patients was 50 ± 12 years, and 75% were female. All echocardiographic features of TV geometry were significantly greater in TR compared to control group. The 3D evaluation of TV annulus showed that the annulus shape was more circular in the TR compared to the control group. When compared patients with moderate and severe TR, there was a significant difference between groups regarding the size of the TV septolateral annulus diameter (3.5 ± 0.4 vs 3.9 ± 0.7 cm; P = .048), and the angle between mitral valve and TV annuluses (12.5 ± 4.3 vs 17 ± 9º; P = .048). Tenting areas measured by 2D echocardiography and obtained by TomTec software were significantly greater in severe TR compared to moderate TR group. The diameter of TV by 2D echocardiography was significantly higher in atrial fibrillation than that in sinus rhythm group among patients with TR.

Conclusions

The implementation of 3D echocardiography is useful in the determination of TV geometry in patients with functional TR. The accurate evaluation of anatomical features of TV might provide valuable tools in the evaluation of patients with functional TR.
International Association of Dental Traumatology guidelines for the management of traumatic dental injuries: General introduction
Authors: Levin Liran , Day Peter F. , Hicks Lamar , O'Connell Anne , Fouad Ashraf F. , Bourguignon Cecilia , Abbott Paul V.
Published: May 2020

Traumatic dental injuries (TDIs) occur most frequently in children and young adults. Older adults also suffer TDIs but at significantly lower rates than individuals in the younger cohorts. Luxation injuries are the most common TDIs in the primary dentition, whereas crown fractures are more commonly reported for the permanent teeth. Proper diagnosis, treatment planning and follow up are very important to assure a favorable outcome. These updates of the International Association of Dental Traumatology's (IADT) Guidelines include a comprehensive review of the current dental literature using EMBASE, MEDLINE, PUBMED, Scopus, and Cochrane Databases for Systematic Reviews searches from 1996 to 2019 and a search of the journal Dental Traumatology from 2000 to 2019. The goal of these guidelines is to provide information for the immediate or urgent care of TDIs. It is understood that some follow‐up treatment may require secondary and tertiary interventions involving dental and medical specialists with experience in dental trauma. As with previous guidelines, the current working group included experienced investigators and clinicians from various dental specialties and general practice. The current revision represents the best evidence based on the available literature and expert opinions. In cases where the published data were not conclusive, recommendations were based on the consensus opinions of the working group. They were then reviewed and approved by the members of the IADT Board of Directors. It is understood that guidelines are to be applied using careful evaluation of the specific clinical circumstances, the clinician's judgment, and the patient's characteristics, including the probability of compliance, finances and a clear understanding of the immediate and long‐term outcomes of the various treatment options vs non‐treatment. The IADT does not, and cannot, guarantee favorable outcomes from adherence to the Guidelines. However, the IADT believes that their application can maximize the probability of favorable outcomes.
The miR‐155/GATA3/IL37 axis modulates the production of proinflammatory cytokines upon TNF‐α stimulation to affect psoriasis development
Authors: Wang Haizhen , Zhang Yujin , Luomei Junzi , Huang Pan , Zhou Rong , Peng Youhua
Published: May 2020

Psoriasis is a recrudescent chronic immune‐mediated inflammatory dermatosis; the production and release of proinflammatory cytokines/chemokines such as TNF‐α has been regarded as critical issues during psoriasis pathogenesis. Based on online microarray profiles, the expression of the transcription factor GATA3 was downregulated in psoriasis lesion tissues. In the present study, we searched for miRNAs that might be related to TNF‐α and GATA3 to investigate an in‐depth understanding of psoriasis pathogenesis. Herein, higher TNF‐α and GATA3 protein levels were observed in psoriasis lesion tissues and that GATA3 overexpression significantly reverses TNF‐α‐induced increases within the production of IL‐6 and CXCL8 in keratinocytes. TNF‐α stimulation increases miR‐155 expression dose‐independently, and the miR‐155 inhibitor significantly reverses TNF‐α‐induced suppression of GATA3 protein levels and increases IL‐6 and CXCL8 production. miR‐155 could suppress the expression of GATA3 by targeting its 3′UTR, while GATA3 could activate the transcription of IL37 by targeting its promoter region. miR‐155 overexpression reduces IL37 protein and increases CXCL8 production; GATA3 overexpression might significantly attenuate the effects of miR‐155 overexpression. In contrast to GATA3, miR‐155 expression is significantly upregulated in psoriasis lesion tissue and is negatively correlated with GATA3 and IL37. In summary, the miR‐155/GATA3/IL37 axis modulates the production of IL‐6 and CXCL8 upon TNF‐α stimulation to affect psoriasis development. Thus, miR‐155/GATA3/IL37 may be potent targets for psoriasis treatment, which needs further in vivo and clinical investigation.
Japanese encephalitis virus – exploring the dark proteome and disorder–function paradigm
Authors: Bhardwaj Taniya , Saumya Kumar Udit , Kumar Prateek , Sharma Nitin , Gadhave Kundlik , Uversky Vladimir N. , Giri Rajanish
Published: May 2020

Japanese encephalitis virus (JEV) is one of the major causes of viral encephalitis all around the globe. Approximately 3 billion people in endemic areas are at risk of Japanese encephalitis. To develop a wholistic understanding of the viral proteome, it is important to investigate both its ordered and disordered proteins. However, the functional and structural significance of disordered regions in the JEV proteome has not been systematically investigated as of yet. To fill this gap, we used here a set of bioinformatics tools to analyze the JEV proteome for the predisposition of its proteins for intrinsic disorder and for the presence of the disorder‐based binding regions (also known as molecular recognition features, MoRFs). We also analyzed all JEV proteins for the presence of the probable nucleic acid‐binding (DNA and RNA) sites. The results of these computational studies are experimentally validated using JEV capsid protein as an illustrative example. In agreement with bioinformatic analysis, we found that the N‐terminal region of the JEV capsid (residues 1–30) is intrinsically disordered. We showed that this region is characterized by the temperature response typical for highly disordered proteins. Furthermore, we have experimentally shown that this disordered N‐terminal domain of a capsid protein has a noticeable ‘gain‐of‐structure’ potential. In addition, using DOPS liposomes, we demonstrated the presence of pronounced membrane‐mediated conformational changes in the N‐terminal region of JEV capsid. In our view, this disorder‐centric analysis would be helpful for a better understanding of the JEV pathogenesis.
Quantifying microbial growth and carbon use efficiency in dry soil environments via 18O water vapor equilibration
Authors: Canarini Alberto , Wanek Wolfgang , Watzka Margarete , Sandén Taru , Spiegel Heide , Šantrůček Jiří , Schnecker Jörg
Published: May 2020

Soil microbial physiology controls large fluxes of C to the atmosphere, thus, improving our ability to accurately quantify microbial physiology in soil is essential. However, current methods to determine microbial C metabolism require liquid water addition, which makes it practically impossible to measure microbial physiology in dry soil samples without stimulating microbial growth and respiration (namely, the “Birch effect”). We developed a new method based on in vivo 18O‐water vapor equilibration to minimize soil rewetting effects. This method allows the isotopic labeling of soil water without direct liquid water addition. This was compared to the main current method (direct 18O‐liquid water addition) in moist and air‐dry soils. We determined the time kinetics and calculated the average 18O enrichment of soil water over incubation time, which is necessary to calculate microbial growth from 18O incorporation in genomic DNA. We tested isotopic equilibration patterns in three natural and six artificially constructed soils covering a wide range of soil texture and soil organic matter content. We then measured microbial growth, respiration and carbon use efficiency (CUE) in three natural soils (either air‐dry or moist). The proposed 18O‐vapor equilibration method provided similar results as the current method of liquid 18O‐water addition when used for moist soils. However, when applied to air‐dry soils the liquid 18O‐water addition method overestimated growth by up to 250%, respiration by up to 500%, and underestimated CUE by up to 40%. We finally describe the new insights into biogeochemical cycling of C that the new method can help uncover, and we consider a range of questions regarding microbial physiology and its response to global change that can now be addressed.