bluuebunny/crossref_metadata_2025 huggingface dataset:
Association ofCXCR6with COVID-19 severity: Delineating the host genetic factors in transcriptomic regulation
Authors: Dai Yulin , Wang Junke , Jeong Hyun-Hwan , Chen Wenhao , Jia Peilin , Zhao Zhongming
Published: February 2021

Background

The coronavirus disease 2019 (COVID-19) is an infectious disease that mainly affects the host respiratory system with ∼80% asymptomatic or mild cases and ∼5% severe cases. Recent genome-wide association studies (GWAS) have identified several genetic loci associated with the severe COVID-19 symptoms. Delineating the genetic variants and genes is important for better understanding its biological mechanisms.

Methods

We implemented integrative approaches, including transcriptome-wide association studies (TWAS), colocalization analysis and functional element prediction analysis, to interpret the genetic risks using two independent GWAS datasets in lung and immune cells. To understand the context-specific molecular alteration, we further performed deep learning-based single cell transcriptomic analyses on a bronchoalveolar lavage fluid (BALF) dataset from moderate and severe COVID-19 patients.

Results

We discovered and replicated the genetically regulated expression ofCXCR6andCCR9genes. These two genes have a protective effect on the lung and a risk effect on whole blood, respectively. The colocalization analysis of GWAS andcis-expression quantitative trait loci highlighted the regulatory effect onCXCR6expression in lung and immune cells. In the lung resident memory CD8+T (TRM) cells, we found a 3.32-fold decrease of cell proportion and lower expression ofCXCR6in the severe than moderate patients using the BALF transcriptomic dataset. Pro-inflammatory transcriptional programs were highlighted in TRMcells trajectory from moderate to severe patients.

Conclusions

CXCR6from the3p21.31locus is associated with severe COVID-19.CXCR6tends to have a lower expression in lung TRMcells of severe patients, which aligns with the protective effect ofCXCR6from TWAS analysis. We illustrate one potential mechanism of host genetic factor impacting the severity of COVID-19 through regulating the expression ofCXCR6and TRMcell proportion and stability. Our results shed light on potential therapeutic targets for severe COVID-19.
Inferring population histories for ancient genomes using genome-wide genealogies
Authors: Speidel Leo , Cassidy Lara , Davies Robert W. , Hellenthal Garrett , Skoglund Pontus , Myers Simon R.
Published: February 2021

Ancient genomes anchor genealogies in directly observed historical genetic variation, and contextualise ancestral lineages with archaeological insights into their geography and lifestyles. We introduce an extension of theRelatealgorithm to incorporate ancient genomes and reconstruct the joint genealogies of 14 previously published high-coverage ancients and 278 present-day individuals of the Simons Genome Diversity Project. As the majority of ancient genomes are of lower coverage and cannot be directly built into genealogies, we additionally present a fast and scalable method,Colate,for inferring coalescence rates between low-coverage genomes without requiring phasing or imputation. Our method leverages sharing patterns of mutations dated using a genealogy to construct a likelihood, which is maximised using an expectation-maximisation algorithm. We applyColateto 430 ancient human shotgun genomes of >0.5x mean coverage. UsingRelateandColate,we characterise dynamic population structure, such as repeated partial population replacements in Ireland, and gene-flow between early farmer and European hunter-gatherer groups. We further show that the previously reported increase in the TCC/TTC mutation rate, which is strongest in West Eurasians among present-day people, was already widespread across West Eurasia in the Late Glacial Period ~10k - 15k years ago, is strongest in Neolithic and Anatolian farmers, and is remarkably well predicted by the coalescence rates between other genomes and a 10,000-year-old Anatolian individual. This suggests that the driver of this signal originated in ancestors of ancient Anatolia >14k years ago, but was already absent by the Mesolithic and may indicate a genetic link between the Near East and European hunter-gatherer groups in the Late Paleolithic.
Emotional arousal impairs association memory: roles of prefrontal cortex regions
Authors: Fujiwara Esther , Madan Christopher R. , Caplan Jeremy B. , Sommer Tobias
Published: February 2021

The brain processes underlying impairing effects of emotional arousal on associative memory were previously attributed to two dissociable routes using high-resolution fMRI of the MTL (Madan et al. 2017). Extrahippocampal MTL regions supporting associative encoding of neutral pairs suggested unitization; conversely, associative encoding of negative pairs involved compensatory hippocampal activity. Here, whole-brain fMRI revealed prefrontal contributions: dmPFC was more involved in hippocampal-dependent negative pair learning and vmPFC in extrahippocampal neutral pair learning. Successful encoding of emotional memory associations may require emotion regulation/conflict resolution (dmPFC), while neutral memory associations may be accomplished by anchoring new information to prior knowledge (vmPFC).
Urban development project goals and the role of professional ignorance: ambiguous policy objectives and their consequences
Authors: Styhre Alexander , Brorström Sara
Published: February 2021

Purpose

Drawing on the literature on professional ignorance, here defined in affirmative terms as the capacity to act regardless of the incompleteness of available information in organizations and professional communities, the article reports empirical material from an urban development project wherein policy makers' instructions are vague and, in certain domains, inconsistent with market conditions.

Design/methodology/approach

Urban development projects regularly include uncertainty and risk taking, and policy makers' stated objectives regarding project goals may be incomplete or merely signal a political ambition. In such situations, first-line project participants need to make decisions as if uncertainties regarding policy objectives are manageable and preferably minimal. The purpose of the article is to substantiate the proposition that professional ignorance is a key mechanism in incomplete or imperfect governance systems.

Findings

Project participants actively questioned policy but acted on the instructions just the same, which is indicative of how professional ignorance is supportive of governance system that relies on first-line market actors and agencies to implement also incomplete or vaguely stated policy objectives. Incomplete policies derive from challenges in political deliberation and bargaining processes, uncertainty regarding the future and shifting preferences among policy makers and constituencies more widely. In practice, incomplete policies regularly include issues for first-level actors (e.g. on the urban development project level) to handle and to reconcile in their day-to-day work.

Originality/value

On basis of an empirical study of a major urban development project, the study contributes to a growing literature that recognizes the value of professional ignorance in governance systems and in project management practice. The study invites further scholarly research that takes an affirmative of professional ignorance but without overlooking its risks and potential malfunctions.
Experimental investigation on WEDM performance analysis using grey-fuzzy integrated with TLBO algorithm for Inconel 625: comparison with GA and SA
Authors: Kumar Anshuman , Upadhyay Chandramani , Shashikant Shashikant
Published: February 2021

Purpose

In the present study, wire electro-discharge machining (WEDM) of Inconel 625 (In-625) is performed with the machining parameter such as spark-on time, spark-off time, wire-speed, wire tension and servo voltage. The purpose of this study is to find the most favorable machining parameter setting with respect to WEDM performance such as material removal rate (MRR) and surface roughness (RA).

Design/methodology/approach

Taguchi’s L27 orthogonal array has been used to design the experiments with varying machining parameters into three-level four factors. A hybrid multi-optimization technique has been purposed with grey relation analysis and fuzzy inference system integrated with teaching learning-based optimization to achieve optimum machinability (MRR and RA in present case). The obtained result has been compared with two evolutionary optimization tools via a genetic algorithm and simulated annealing.

Findings

It has been found that proposed hybrid technique taking minimum computational time, provide better solution and avoid priority weightage calculation by decision-makers. A confirmation test has been performed at single and multi-optimal parameter settings. The decision-makers have been chosen to select any single or multi-parameter setting as per the industry’s demand.

Originality/value

The proposed optimization technique provides better machinability of In-625 using zinc-coated brass wire electrode during WEDM operation.
The multilevel analysis of students’ achievement: Evidence from Morocco
Authors: Chatri Abdellatif , Chahbi Otman , Snihji Mustapha
Published: February 2021

This paper, using multi‐level modelling, sought to highlight student‐level and school‐level characteristics that differentiate the academic performance in mathematics from a sample of 6080 Moroccan secondary students who participated in the 2011 Trends in International Mathematics and Science Study (TIMSS) test. The results indicated little evidence to support the Heyneman–Loxley effect, as they showed that individual and family characteristics were the strongest determinants of achievement compared to the schools’ factors. Students scored higher when they were boys, were younger, were more self‐confident, were more ambitious, and felt secure in school. They also scored higher when they came from families with a higher socioeconomic status, particularly when their parents were able to ensure the availability of learning resources, and were of a higher level of education. Finally, schools were matter for their pupil achievement mainly through the location channel, as urban pupils outperformed rural ones. However, the other school characteristics, including those related to teachers, played a negative, or at best neutral, role in pupil outcomes. These findings have important public policy implications. Redesigning education policy towards improving the school's environment and fostering inclusivity would be needed to enhance learning performance of Moroccan students.
Exploring the summer reading effect through visual analysis of multiple datasets
Authors: Reed Deborah K. , Aloe Ariel M. , Park Seohee , Reeger Adam J.
Published: February 2021

Historically, there has been concern about students losing reading ability over extended breaks from school, commonly in the summer, but studies of this phenomenon have produced inconsistent results. We applied exploratory visual analysis of multiple datasets to examine whether students in Grades K‐5 appear to lose or improve in various reading abilities over the summer and across consecutive school years. Archival data were obtained on students of different U.S. school districts who did not participate in a formal summer reading programme. Data were disaggregated by groups considered most vulnerable to summer loss: those from economically disadvantaged backgrounds and those identified with disabilities. Given the variety of measure types and scores, we centred scores on each measure's cut point for proficiency in a particular grade level to depict how students' scores deviated from the proficiency classifications before and after a summer break. Overall, students' scores relative to the benchmark appeared on average to have maintained or improved, and there was no observed accumulated decrement in reading performance across years. For anomalous instances of summer loss, we offer possible alternative explanations such as measurement artefacts and unrehearsed learning. Visual analysis of the datasets suggested that summer breaks were not associated with systematic losses of students' reading ability, even among those considered most vulnerable to the phenomenon. However, available assessments and benchmarks are not designed to measure summer learning specifically, and little is known about the kinds of literacy experiences students not in formal programmes might be having. Thus, more research on summer maturation and degeneration is warranted.
Anti‐PD1 versus anti‐PD‐L1 immunotherapy in first‐line therapy for advanced non‐small cell lung cancer: A systematic review and meta‐analysis
Authors: Brito Angelo Borsarelli Carvalho , Camandaroba Marcos Pedro Guedes , de Lima Vladmir Cláudio Cordeiro
Published: February 2021

Background

Due to the increasing number of trials with immune checkpoint inhibitors (ICIs) in the first‐line therapy of non‐small cell lung cancer (NSCLC) patients, we performed a systematic review and meta‐analyses to investigate the difference between anti PD‐1 and PD‐L1 antibodies, used alone or in combination with chemotherapy, through adjusted indirect analysis to minimize the potential bias regarding overall survival (OS), progression‐free survival (PFS), overall response rate (ORR) and grade 3–5 adverse events (AEs).

Methods

A systematic review of studies reporting clinical outcomes and toxicity associated with first‐line therapy employing anti‐PD1 or anti‐PD‐L1 antibodies alone, or in combination with chemotherapy, to treat metastatic, treatment‐naïve NSCLC patients was performed. Primary outcomes were OS, PFS, ORR and grade 3–5 AEs. We used a random‐effects model to generate pooled estimates for proportions. Meta‐analyses using pooled risk ratios were performed for binary outcomes from comparative studies with the random effects model.

Results

A total of 13 eligible studies met our eligibility criteria, including 7673 patients. In the ICI‐chemotherapy combination subgroup, we observed that anti‐PD1 therapy was associated with better OS (p = 0.022) and PFS (p = 0.029) compared with anti‐PD‐L1 therapy. In the monotherapy subgroup, there was no statistical difference between the use of anti‐PD‐1 and anti‐PD‐L1 for OS and PFS. With regard to ORR and toxicity, in the ICI‐chemotherapy combination subgroup, we observed a trend of better ORR (p = 0.12) with the use of anti‐PD1 therapy and less frequent grade 3–5 AEs compared to the use of anti‐PD‐L1 therapy (p = 0.0302). In the monotherapy subgroup, there was no statistical difference between the use of anti‐PD‐1 and anti‐PD‐L1 regarding ORR and toxicity.

Conclusions

Our study suggests that PD‐1 drug plus chemotherapy is superior to anti‐PD‐L1 plus chemotherapy for NSCLC; nevertheless, as monotherapy, both strategies appear to be similar.
Metabolome analysis reveals important compounds related to dwarfing effect of interstock on scion in pear
Authors: Cui Zhenhua , Zhang Huan , Galarneau Erin R.‐A. , Yang Yingjie , Li Dingli , Song Jiankun , Ma Chunhui , Zhang Shaoling , Wang Ran
Published: February 2021

The utilisation of interstocks or rootstocks to reduce tree size has long been used in orchards. In the present study, we characterised the dwarfing effect of “OHF51” (Pyrus communis “Old Home” × “Farmingdale”) when used as interstock compared with callery pear (Pyrus calleryana Decne.). Shorter trees, smaller canopy, smaller trunk diameter and lower height of the first branch were found in trees with “OHF51” as the interstock as compared to callery pear. Metabolome analysis showed that the interstock altered the metabolite profiles of both the scion and the rootstock. The number of identified differential metabolites in scions, interstocks and roots were 8, 39 and 12, respectively, with “OHF51” interstock as compared to the same positions with callery as the interstock. Flavonoids and phenolic acids/derivatives were most altered in concentration. The concentrations of flavonoids procyanidin B2 and procyanidin B3 were remarkably higher in both the scion shoots and the interstock because of “OHF51,” while the concentration of two monosucroses, D‐sorbitol and D‐mannitol, were drastically reduced in roots with “OHF51” interstock present. The reallocation of carbohydrates from shoot to root could be influenced by the interstock, which participates in the regulation of scion growth in the spring season. Flavonoids and phenolic acids/derivatives are understood to be key compounds involved in the reduction of scion growth.
Need‐resource indicators and nonprofit human services organization density
Authors: Sevak Kunal Y. , Baker LaKami
Published: February 2021

The challenges facing the US nonprofit human services organizations (NHSOs) in securing philanthropic resources and the resulting pressure for increased commercialization are well‐known in the nonprofit literature. However, there is still limited research on how such financial challenges are likely to affect their location choices, particularly in a post‐recession context. Using organizational ecology theory, we conducted a nationwide longitudinal study covering the period of the US 2008 recession to examine whether resource availability is more likely to predict the density of NHSOs than human needs. We used secondary data on a variety of socioeconomic variables from the National Center for Charitable Statistics and the US census survey in a linear multivariate regression analysis. The findings supported a majority of hypotheses, suggesting that NHSOs pursuing earned income are less (versus more) likely to be established in regions where the socioeconomic factors indicate a high (versus low) level of human needs. These findings suggest a counterintuitive trend in the establishment of NHSOs and present cautionary information on pursuing commercial activities in the human services sector.
A consequentialist ethical analysis of federal funding of elective abortions
Authors: Gleeson Emile I. , Guerrini Christi J.
Published: February 2021

Insurance coverage of abortion varies widely across the United States and is an extensively debated issue. Medicaid coverage of abortion is particularly relevant because the majority of abortion patients are poor or low‐income and are thus often covered by Medicaid. Since the Hyde Amendment was first passed in 1976, federal Medicaid funds have been banned from covering the costs of elective abortion. Although states are allowed to use their own funds to cover abortions for their Medicaid recipients, only 17 states currently do so. Of these 17 states, only five cover abortion costs voluntarily; the others do so pursuant to court order. The medical literature includes few ethical analyses of the Hyde Amendment’s ban on Medicaid funding of elective abortions. To fill this gap, we perform an ethical analysis of federal policy to fund elective abortions using a consequentialist approach focused on consequences for pregnant women and their children.
Identifying regions of inhomogeneities in spatial processes via an M‐RA and mixture priors
Authors: Benedetti Marco H. , Berrocal Veronica J. , Narisetty Naveen N.
Published: February 2021

Soils have been heralded as a hidden resource that can be leveraged to mitigate and address some of the major global environmental challenges. Specifically, the organic carbon stored in soils, called soil organic carbon (SOC), can, through proper soil management, help offset fuel emissions, increase food productivity, and improve water quality. As collecting data on SOC are costly and time‐consuming, not much data on SOC are available, although understanding the spatial variability in SOC is of fundamental importance for effective soil management. In this manuscript, we propose a modeling framework that can be used to gain a better understanding of the dependence structure of a spatial process by identifying regions within a spatial domain where the process displays the same spatial correlation range. To achieve this goal, we propose a generalization of the multiresolution approximation (M‐RA) modeling framework of Katzfuss originally introduced as a strategy to reduce the computational burden encountered when analyzing massive spatial datasets. To allow for the possibility that the correlation of a spatial process might be characterized by a different range in different subregions of a spatial domain, we provide the M‐RA basis functions weights with a two‐component mixture prior with one of the mixture components a shrinking prior. We call our approach the mixture M‐RA. Application of the mixture M‐RA model to both stationary and nonstationary data show that the mixture M‐RA model can handle both types of data, can correctly establish the type of spatial dependence structure in the data (e.g., stationary versus not), and can identify regions of local stationarity.
Nbs1‐mediated DNA damage repair pathway regulates haematopoietic stem cell development and embryonic haematopoiesis
Authors: Chen Yu , Sun Jie , Ju Zhenyu , Wang Zhao‐Qi , Li Tangliang
Published: February 2021

Objectives

DNA damages pose threats to haematopoietic stem cells (HSC) maintenance and haematopoietic system homeostasis. Quiescent HSCs in adult mouse bone marrow are resistant to DNA damage, while human umbilical cord blood‐derived proliferative HSCs are prone to cell death upon ionizing radiation. Murine embryonic HSCs proliferate in foetal livers and divide symmetrically to generate HSC pool. How murine embryonic HSCs respond to DNA damages is not well‐defined.

Materials and methods

Mice models with DNA repair molecule Nbs1 or Nbs1/p53 specifically deleted in embryonic HSCs were generated. FACS analysis, in vitro and in vivo HSC differentiation assays, qPCR, immunofluorescence and Western blotting were used to delineate roles of Nbs1‐p53 signaling in HSCs and haematopoietic progenitors.

Results

Nbs1 deficiency results in persistent DNA breaks in embryonic HSCs, compromises embryonic HSC development and finally results in mouse perinatal lethality. The persistent DNA breaks in Nbs1 deficient embryonic HSCs render cell cycle arrest, while driving a higher rate of cell death in haematopoietic progenitors. Although Nbs1 deficiency promotes Atm‐Chk2‐p53 axis activation in HSCs and their progenies, ablation of p53 in Nbs1 deficient HSCs accelerates embryonic lethality.

Conclusions

Our study discloses that DNA double‐strand repair molecule Nbs1 is essential in embryonic HSC development and haematopoiesis. Persistent DNA damages result in distinct cell fate in HSCs and haematopoietic progenitors. Nbs1 null HSCs tend to be maintained through cell cycle arrest, while Nbs1 null haematopoietic progenitors commit cell death. The discrepancies are mediated possibly by different magnitude of p53 signaling.
Point‐of‐care ultrasound during the COVID‐19 pandemic: A multidisciplinary approach between intensivists and echocardiographers
Authors: Yuriditsky Eugene , Saric Muhamed , Horowitz James M.
Published: February 2021

Purpose

The coronavirus disease‐2019 (COVID‐19) led to a large influx of critically ill patients and altered echocardiography laboratory workflow. We developed a point‐of‐care ultrasound (POCUS) first approach to patients requiring echocardiography and describe our workflow and findings.

Methods

We performed a single‐center retrospective analysis of all POCUS studies performed on critically ill patients with COVID‐19. Sonography was performed by intensivists, uploaded and archived, and rapidly reviewed by echocardiographers. We evaluated each study based on the number of views obtained. Additionally, we provide a description of the workflow during the COVID‐19 surge at a tertiary care hospital in New York City.

Results

Fifty patients had POCUS studies performed by intensivists and reviewed by echocardiographers obviating the need for sonographer‐performed studies. Of the 48 cardiac POCUS studies, 17% of patients had 4 of 4 standard views available while 53% had 3 of 4 standard views. The parasternal long‐axis view was obtained on 81%, subxiphoid view on 79%, apical 4‐chamber view on 71%, and parasternal short‐axis view on 63% of patients.

Conclusions

Our POCUS workflow allowed intensivists to perform cardiac sonography for rapid bedside diagnosis of pathology with immediate interpretation performed by echocardiographers. At least 3 views were obtained in the majority of cases.
Lagged and dormant season climate better predict plant vital rates than climate during the growing season
Authors: Evers Sanne M. , Knight Tiffany M. , Inouye David W. , Miller Tom E. X. , Salguero‐Gómez Roberto , Iler Amy M. , Compagnoni Aldo
Published: February 2021

Understanding the effects of climate on the vital rates (e.g., survival, development, reproduction) and dynamics of natural populations is a long‐standing quest in ecology, with ever‐increasing relevance in the face of climate change. However, linking climate drivers to demographic processes requires identifying the appropriate time windows during which climate influences vital rates. Researchers often do not have access to the long‐term data required to test a large number of windows, and are thus forced to make a priori choices. In this study, we first synthesize the literature to assess current a priori choices employed in studies performed on 104 plant species that link climate drivers with demographic responses. Second, we use a sliding‐window approach to investigate which combination of climate drivers and temporal window have the best predictive ability for vital rates of four perennial plant species that each have over a decade of demographic data (Helianthella quinquenervis, Frasera speciosa, Cylindriopuntia imbricata, and Cryptantha flava). Our literature review shows that most studies consider time windows in only the year preceding the measurement of the vital rate(s) of interest, and focus on annual or growing season temporal scales. In contrast, our sliding‐window analysis shows that in only four out of 13 vital rates the selected climate drivers have time windows that align with, or are similar to, the growing season. For many vital rates, the best window lagged more than 1 year and up to 4 years before the measurement of the vital rate. Our results demonstrate that for the vital rates of these four species, climate drivers that are lagged or outside of the growing season are the norm. Our study suggests that considering climatic predictors that fall outside of the most recent growing season will improve our understanding of how climate affects population dynamics.
A latitudinal gradient of microbial β‐diversity in continental paddy soils
Authors: Xiao Xian , Zhang Na , Ni Haowei , Yang Yunfeng , Zhou Jizhong , Sun Bo , Liang Yuting
Published: February 2021

Aim

The β‐diversity of plants and animals generally decreases with increasing latitudes. Here, we tested whether this relationship also holds for soil microbes at both functional and taxonomic levels.

Location

China.

Time period

Between June and October 2013.

Major taxa studied

Soil archaea, bacteria, and functional genes.

Methods

We used a spatially explicit ‘L‐shaped’ sampling strategy in 39 paddy fields in China to study the pattern of soil microbial β‐diversity (i.e., species turnover, βz) across a latitudinal gradient (19.75° N to 47.58° N), with 11 soil samples taken within a 100 m × 100 m plot from each field. Archaeal and bacterial communities were analysed by sequencing 16S ribosomal RNA gene amplicons using Illumina MiSeq; microbial functional genes involved in C/N/P/S cycling were detected by GeoChip.

Results

We showed that the microbial β‐diversity varied considerably across taxonomic and functional groups. For both soil microbial communities and functional genes, β‐diversity decreased significantly along elevated latitudes at the continental scale. Woesearchaeota of archaeal communities, Bacteroidetes of bacterial communities, and the functional genes involved in methane production displayed the greatest decreases. Both mean temperature during the growing season of rice plants and paddy soil heterogeneity contributed to the latitudinal patterns. Further analyses indicated that temperature was more important than soil heterogeneity in driving the β‐diversity of microbial communities and functional genes.

Main conclusions

These results highlight the importance of temperature‐driven soil microbial β‐diversity and suggest the potential to predict the changes of microbial diversity with climate change.
Refocusing dental care: A risk‐based preventative oral health programme for dentate older people in UK care homes
Authors: Patel Rakhee , Fitzgerald Richard , Warburton Fiona , Robertson Claire , Pitts Nigel B. , Gallagher Jennifer E
Published: February 2021

Background

There is strong evidence for managing the risk of dental caries, notably dose‐dependent use of fluoride based on risk. Specific guidance is lacking on higher fluoride use in older people in care homes and prevention is often omitted from dental care plans.

Objectives

To introduce a risk‐based preventative approach to existing routine dental care for older people in care homes.

Methods

Three mixed residential and nursing care homes for the frail and elder (>65 years) were selected to participate. All residents were risk assessed based on dependency, dentition status and self‐care abilities and consequently placed on the appropriate evidence‐based intervention (2800 ppm high dose fluoride toothpaste and/or quarterly fluoride varnish placement). Full mouth ICDAS dental examinations were completed at baseline, 6 months and 12 months.

Results

At baseline, 127 risk assessments were completed in which most dentate residents (58.2%, n = 74) were assessed as Risk Level 2/3 (mod/high) whilst edentulous residents were all Risk Level 1 (low) (41.7%, n = 53). Only 13 (26.5%) of the 49 eligible residents completed the 12‐month preventative programme. There was a significant difference in root caries (P < .0001), with 17 (51.5%) root lesions changing from active at baseline to arrested at 12 months.

Conclusions

The findings provide early indication of fluoride efficacy, especially on root caries in this vulnerable group, and highlight the challenges of delivering programme's in these complex, changing environments.
The networked refugee: The role of transnational networks in the journeys across the Mediterranean
Authors: D'Angelo Alessio
Published: February 2021

The experience of migrants crossing the Mediterranean has been represented as that of passive components of large‐scale human flows driven by conflicts, migration policies and smuggling. This article proposes a reflection on the advantages of using a social network lens to better understand these experiences at a micro‐ and meso‐level, bringing to the fore the personal and relational dimensions. By examining the narratives of people who reached the coasts of Sicily (Italy) via the Libyan route, the article highlights the key role of local and transnational ties at every single juncture of these very long, often serendipitous journeys. The concept of ‘journey’ is used to frame this analysis, but also to debunk some of the deterministic, static and Euro‐centred assumptions, which have characterized mainstream narratives and some scholarly debates. Thus, the refugee journey emerges as a fluid process characterized by the continuous deconstruction and reconstruction of social networks.
Shortening the paediatric Haemophilia Activities List (pedHAL) based on pooled data from international studies
Authors: Kuijlaars Isolde A. R. , van der Net Janjaap , Bouskill Vanessa , Hilliard Pamela , Juodyte Agne , Khair Kate , Trakymiene Sonata Saulyte , Fischer Kathelijn
Published: February 2021

Introduction

The paediatric Haemophilia Activities List (pedHAL) was developed to measure activities and participation in children and youth with haemophilia. Results from international studies provide an opportunity to determine which items are universally important.

Aim

The aim of this study was to determine which items of the pedHAL are redundant to construct a shorter version of the pedHAL.

Methods

This study is a cross‐sectional multicentre secondary analysis on pooled data of published studies using the pedHAL (7 domains, 53 items, optimum score: 100) in children with haemophilia A/B aged 4–18 years. To identify redundant items, the following aspects were evaluated: floor and ceiling effects, proportions of missing and ‘not applicable’ responses, inter‐item correlations, component loadings in an exploratory factor analysis, internal consistency and item‐total correlations.

Results

Data on 315 patients with haemophilia from 6 studies were evaluated. Median age was 12.2 years) (range 4.0–18.0), 87.3% had severe haemophilia and 80.3% received prophylaxis. Median (IQR) pedHAL sum score was 96.7 (88.0–100). After a stepwise procedure, 31 items were removed, resulting in a pedHALshort of 22 items, representing all original 7 domains. Most remaining items belonged to the domains ‘sitting/kneeling/standing’ and ‘functions of the legs’. The pedHALshort sum score was similar to the original pedHAL sum score, with small differences in 5 domains.

Conclusion

This clinimetric study resulted in >50% reduction of the length of the pedHAL. The 22‐item pedHALshort reduces patient burden and is expected to capture the information on activities and participation. The pedHALshort needs validation in other populations.
Dysregulation of sphingolipid metabolic enzymes leads to high levels of sphingosine‐1‐phosphate and ceramide in human hepatocellular carcinoma
Authors: Miura Kohei , Nagahashi Masayuki , Prasoon Pankaj , Hirose Yuki , Kobayashi Takashi , Sakata Jun , Abe Manabu , Sakimura Kenji , Matsuda Yasunobu , Butash Ali L. , Katsuta Eriko , Takabe Kazuaki , Wakai Toshifumi
Published: February 2021

Aim

Sphingosine‐1‐phosphate (S1P) and ceramide are bioactive sphingolipids known to be important in regulating numerous processes involved in cancer progression. The aim of this study was to determine the absolute levels of sphingolipids in hepatocellular carcinoma (HCC) utilizing data obtained from surgical specimens. In addition, we explored the clinical significance of S1P in patients with HCC and the biological role of S1P in HCC cells.

Methods

Tumors and normal liver tissues were collected from 20 patients with HCC, and sphingolipids were measured by mass spectrometry. The Cancer Genome Atlas (TCGA) cohort was utilized to evaluate gene expression of enzymes related to sphingolipid metabolism. Immunohistochemistry of phospho‐sphingosine kinase 1 (SphK1), an S1P‐producing enzyme, was performed for 61 surgical specimens. CRISPR/Cas9‐mediated SphK1 knockout cells were used to examine HCC cell biology.

Results

S1P levels were substantially higher in HCC tissue compared with normal liver tissue. Levels of other sphingolipids upstream of S1P in the metabolic cascade, such as sphingomyelin, monohexosylceramide and ceramide, were also considerably higher in HCC tissue. Enzymes involved in generating S1P and its precursor, ceramide, were found in higher levels in HCC compared with normal liver tissue. Immunohistochemical analysis found that phospho‐SphK1 expression was associated with tumor size. Finally, in vitro assays indicated that S1P is involved in the aggressiveness of HCC cells.

Conclusions

Sphingolipid levels, including S1P and ceramide, were elevated in HCC compared with surrounding normal liver tissue. Our findings suggest S1P plays an important role in HCC tumor progression, and further examination is warranted.
NK cells in antibody‐mediated rejection – Key effector cells in microvascular graft damage
Authors: O’Neill Megan A. , Hidalgo Luis G.
Published: February 2021

Antibody‐mediated rejection (ABMR) stands as the major limitation to long‐term transplant outcome. The immunologic understanding of ABMR continues to progress and has identified natural killer (NK) cells as key effector cells promoting and coordinating the immune attack on the graft microvascular endothelium. This review discusses the current concepts outlining the different ways that allow for NK cell recognition of graft endothelial cells which includes antibody‐dependent as well as independent processes.
Reference intervals of white blood cell parameters for healthy adults in japan
Authors: Takami Akiyoshi , Watanabe Shinichiro , Yamamoto Yoshikazu , Miyachi Hayato , Bamba Yukiharu , Ohata Masahiko , Mishima Seiji , Kubota Hiroshi , Nishiura Akihiko , Inaba Tohru , Enomoto Megumi , Mitsuhashi Takayuki , Nakanishi Kayoko , Miura Reiko , Nonaka Emi , Shimbo Kei , Yatomi Yutaka , Tohyama Kaoru ,   The Japanese Society for Laboratory Hematology subcommittee on Standardization of Blood Cell Morphology (JSLH‐SBCM)
Published: February 2021

Introduction

While white blood cell (WBC) parameters have been suggested to depend on ethnicity and gender, reference intervals in healthy Asian populations are limited. The present study established reference intervals of WBC parameters for healthy adults in Japan.

Methods

A total of 750 healthy adults (447 women and 303 men; 18‐67 years old, median 40 years old) at 7 Japanese centers who participated in regular medical checkups entered this study. The WBC parameters were measured using automated hematocytometers and blood film reviews by a manual microscopic examination.

Results

The reference intervals of the WBC parameters according to gender in healthy adults were determined. Age‐specific decreases in WBC counts of both gender groups and in neutrophil counts of women were noted. Favorable correlations between the hematocytometer and microscopic methods were found in neutrophils, lymphocytes, and eosinophils but not in monocytes or basophils.

Conclusion

This study suggests the need to consider gender and age in the clinical use of reference intervals of WBC parameters.
Automatic identification of knowledge‐transforming content in argument essays developed from multiple sources
Authors: Raković Mladen , Winne Philip H. , Marzouk Zahia , Chang Daniel
Published: February 2021

Developing knowledge‐transforming skills in writing may help students increase learning by actively building knowledge, regardless of the domain. However, many undergraduate students struggle to transform knowledge when drafting essays based on multiple sources. Writing analytics can be used to scaffold knowledge transforming as writers bring evidence to bear in supporting claims. We investigated how to automatically identify sentences representing knowledge transformation in argumentative essays. A synthesis of cognitive theories of writing and Bloom's typology identified 22 linguistic features to model processes of knowledge transforming in a corpus of 38 undergraduates' essays. Findings indicate undergraduates mostly paraphrase or copy information from multiple sources rather than engage deeply with sources' content. Eight linguistic features were important for discriminating evidential sentences as telling versus transforming source knowledge. We trained a machine learning algorithm that accurately classified nearly three of four evidential sentences as knowledge‐telling or knowledge‐transforming, offering potential for use in future research.
Caregivers' experiences of medication management advice for people living with dementia at discharge
Authors: Sawan Mouna J. , Jeon Yun‐Hee , Bond Christine , Hilmer Sarah N. , Chen Timothy F. , Wennekers Damian , Gnjidic Danijela
Published: February 2021

Rationale, Aims, and Objectives

Caregivers of people living with dementia play an essential role in managing medications across transitions of care. Adequate caregiver medication management guidance at hospital discharge is important to ensure optimal outcomes from medication use. This qualitative study explores the experiences and perspectives of caregivers about the medication management guidance provided at hospital discharge.

Methods

A qualitative approach using semi‐structured, telephone interviews was conducted with 31 caregivers of people with dementia across Australia. Purposive sampling was used to ensure maximum variation of diverse experiences and perspectives.

Results

Caregivers' experiences of medication guidance for people with dementia at discharge were described in three themes including: (a) inadequate information about medication management at discharge; (b) limited caregiver engagement in medication management decisions; and (c) difficulties ensuring medication supply post discharge. Most participants indicated they would like to be included in discussions at discharge. However, participation was influenced by caregivers being overwhelmed by discharge processes; proactively seeking information on medication‐related harm; and belief in advocacy as part of their caregiver role. Caregivers reported they would like to receive a tailored medication list for people with dementia which included information on medications that may impact on the patient's cognition, and for hospital staff to communicate with both the community pharmacist and primary care physician, to improve co‐ordination post transition.

Discussion

In our study of caregivers of people with dementia, we identified key recommendations to facilitate regular participation of people living with dementia and their caregiver around medication guidance at discharge.
Association of dietary insulinaemic potential and odds of non‐alcoholic fatty liver disease among adults: A case–control study
Authors: Sohouli Mohammad Hassan , Sayyari Ali Akbar , Lari Abolfazl , Nameni Ghazaleh , Lotfi Mojtaba , Fatahi Somaye , Saneie Solaleh , Găman Mihnea‐Alexandru , Moodi Farzan , Raee Pourya , Aghamiri Shahin , Rayi Appaji , Shahriari Ali , Moodi Vihan
Published: February 2021

Background

Hyperinsulinaemia is considered as a major risk factor for the development of a myriad of chronic diseases. We examined the association between the dietary insulinaemic potential and the odds of non‐alcoholic fatty liver disease (NAFLD) among Iranian adults.

Methods

After being subjected to a liver ultrasound, 166 patients with NAFLD and 200 controls were included in the study. The dietary intakes and the physical activity levels of the participants were evaluated using a validated semi‐quantitative food frequency questionnaire and the International Physical Activity Questionnaire (short IPAQ), respectively. The insulinaemic potential of the diet was assessed by computing the scores of the Empirical Dietary Index for Hyperinsulinemia (EDIH) and the Empirical Dietary Index for Insulin Resistance (EDIR).

Results

Compared with the control subjects, patients with NAFLD were significantly older; had higher values for body mass index, fasting blood sugar, triglycerides, low‐density lipoprotein cholesterol, total cholesterol and alanine transaminase; and were more likely to smoke. Moreover, NAFLD patients had significant lower levels of high‐density lipoprotein cholesterol and were less likely to perform physical activity. The risk of NAFLD was higher in the individuals in the highest tertile of the EDIH (odds ratio [OR] = 2.79; 95% confidence interval [CI] = 1.32–5.90; p value for trend < 0.05) and EDIR (OR = 2.42; 95% CI = 1.22‐4.79; p value for trend < 0.05) compared to those in the lowest tertile of these scores.

Conclusions

Our study indicates that a higher dietary insulinaemic potential is associated with an increased risk of NAFLD.
THE REAL EXCHANGE RATE AND DEVELOPMENT THEORY, EVIDENCE, ISSUES AND CHALLENGES
Authors: Demir Firat , Razmi Arslan
Published: February 2021

This paper surveys the theoretical and empirical literature on the effects of the real exchange rate (RER) on international trade, economic development and growth. We summarize the main conceptual issues, briefly discuss the relevance of the RER as an instrument of development policy, provide an overview of the macroeconomic and microeconomic mechanisms that link the RER to trade and long‐run growth and development, analyse the challenges – especially the disconnect between theory and data – that often arise in empirical applications, and discuss new avenues for future research. In the process, we present some updated estimates and illustrative figures. The mechanisms through which the RER influences long‐run growth and structural change remains a promising area of research and the relevance of individual channels in different contexts deserves much more careful investigation. Greater data availability should help fill some of these gaps in our understanding.
Paediatric poisoning presentations reported to a regional toxicology service in Australia
Authors: Downes Michael A , Lovett Caitlyn J , Isbister Geoffrey K
Published: February 2021

Aim

The aim of this study is to describe the epidemiology and health‐care utilisation of paediatric emergency department (ED) presentations due to poisoning.

Methods

A retrospective review of all ED presentations of paediatric poisoning cases (<18 years) reported to a tertiary toxicology service from 2015 to 2016 was conducted. Cases were classified into three age groups: pre‐school (0–6 years), primary school (7–11 years) and adolescent (12–17 years). Outcomes included patient transfer, length of ED stay (LOS) and proportion admitted to a medical ward, mental health unit or intensive care unit (ICU).

Results

From 764 consultations over a 2‐year period, 87 were excluded as non‐ED presentations. From these, there were 194 (29%; 47% female) pre‐school aged, 34 (5%; 41% female) primary school aged and 449 (66%; 77% female) adolescent presentations. Deliberate self‐poisoning was most common in 394 of 449 (88%) adolescents. Accidental exposures accounted for 159 (82%) of pre‐school presentations and natural toxins occurred in all three age groups. Paracetamol, selective serotonin reuptake inhibitors, antipsychotics and ibuprofen were the most common toxins. Discharge from ED occurred in 147 of 194 (76%) pre‐school, 24 of 34 (71%) primary school and 223 of 449 (50%) adolescent presentations. Of the 449 adolescents, 137 (31%) were admitted medically (median LOS 19.9 h), 19 were admitted to ICU (median LOS 71 h) and 70 (16%) admitted to mental health (median LOS 122 h). Five pre‐school aged children were admitted to ICU.

Conclusions

Adolescent deliberate self‐poisoning has a significant impact on hospital resources, with mental health problems requiring extended length of stay. There were fewer pre‐school accidental poisoning consultations, which were mainly discharged from ED.
Impact of equipment and handling on systolic blood pressure measurements in conscious dogs in an animal hospital environment
Authors: Lyberg Maria , Ljungvall Ingrid , Häggström Jens , Ahlund Ellinor , Pelander Lena
Published: February 2021

Background

Situational hypertension and differences between devices complicate interpretations of systolic blood pressure (SBP) measurements in dogs.

Hypothesis/Objectives

To evaluate if time point of in‐clinic SBP measurement, type of oscillometric device, and operator affect SBP measurements in conscious dogs.

Animals

Sixty‐seven privately owned dogs with or without chronic kidney disease, divided into 2 study samples (A and B).

Methods

Cross‐sectional diagnostic study. In part A, SBP measurements in dogs were performed using 2 different devices (HDO and petMap) after acclimatization at 3 standardized time points during a clinical visit. In part B, SBP measurements (HDO) were performed in dogs by a trained final year veterinary student and by the owner alone, at the same occasion.

Results

For all dogs, there was no difference in mean SBP (mSBP) among the 3 time points for HDO (P= .12) or petMAP (P= .67). However, intraindividual mSBP differences of up to 60 mm Hg between time points were documented. Mean SBP obtained with petMAP was on average 14 (95% CI: 8‐20) mm Hg higher than mSBP obtained with HDO, and this difference increased with increasing SBP. Mean SBP measurements obtained by the trained student were 7 (95% CI: 2‐11) mm Hg higher than mSBP measurements obtained by the owner.

Conclusions and Clinical Importance

According to the results of this study, time point of in‐clinic SBP measurement in dogs is of minor importance, and instructing owners to perform measurements might reduce suspected situational hypertension. Differences in mSBP measured with HDO and petMAP underscore the need for validation of BP devices used clinically.