bluuebunny/crossref_metadata_2025 huggingface dataset:
The zinc finger proteins ZC3H20 and ZC3H21 stabilise mRNAs encoding membrane proteins and mitochondrial proteins in insect-formTrypanosoma brucei
Authors: Liu Bin , Marucha Kevin Kamanyi , Clayton Christine
Published: May 2019

ZC3H20 and ZC3H21 are related trypanosome proteins with two C(x)8C(x)5C(x)3H zinc finger motifs. ZC3H20 is unstable in mammalian-infective bloodstream forms, but becomes more abundant as they transform to growth-arrested stumpy form, while ZC3H21 appears only in the procyclic form of the parasite, which infects Tsetse flies. Each protein binds to several hundred mRNAs, with overlapping but not identical specificities. Both increase expression of bound mRNAs, probably through recruitment of the MKT1-PBP1 complex. At least seventy of the bound mRNAs decrease after RNAi targeting ZC3H20 or ZC3H20 and ZC3H21; their products include procyclic-specific proteins of the plasma membrane and energy metabolism. Simultaneous depletion of ZC3H20 and ZC3H21 causes procyclic forms to shrink and stop growing; in addition to decreases in target mRNAs, there are other changes suggestive of loss of developmental regulation. The bloodstream-form specific protein RBP10 controls ZC3H20 and ZC3H21 expression. Interestingly, some ZC3H20/21 target mRNAs also bind to and are repressed by RBP10, allowing for dynamic regulation as RBP10 decreases and ZC3H20 and ZC3H21 increase during differentiation.
Integrative analysis of large-scale loss-of-function screens identifies robust cancer-associated genetic interactions
Authors: Lord Christopher J. , Quinn Niall , Ryan Colm J.
Published: May 2019

Genetic interactions, such as synthetic lethal effects, can now be systematically identified in cancer cell lines using high-throughput genetic perturbation screens. Despite this advance, few genetic interactions have been reproduced across multiple studies and many appear highly context-specific. Understanding which genetic interactions are robust in the face of the molecular heterogeneity observed in tumours and what factors influence this robustness could streamline the identification of therapeutic targets. Here, we develop a computational approach to identify robust genetic interactions that can be reproduced across independent experiments and across non-overlapping cell line panels. We used this approach to evaluate >140,000 potential genetic interactions involving cancer driver genes and identified 1,520 that are significant in at least one study but only 220 that reproduce across multiple studies. Analysis of these interactions demonstrated that: (i) oncogene addiction effects are more robust than oncogene-related synthetic lethal effects; and (ii) robust genetic interactions in cancer are enriched for gene pairs whose protein products physically interact. This suggests that protein-protein interactions can be used not only to understand the mechanistic basis of genetic interaction effects, but also to prioritise robust targets for further development. To explore the utility of this approach, we used a protein-protein interaction network to guide the search for robust synthetic lethal interactions associated with passenger gene alterations and validated two novel robust synthetic lethalities.
AEGIS: An In Silico Tool to model Genome Evolution in Age-Structured Populations
Authors: Bradshaw William J. , Šajina Arian , Valenzano Dario Riccardo
Published: May 2019

AEGIS (Ageing of Evolving Genomes In Silico) is a versatile population-genetics numerical-simulation tool that enables the evolution of life history trajectories under sexual and asexual reproduction and a wide variety of evolutionary constraints. By encoding age-specific survival and reproduction probabilities as discrete genomic elements, AEGIS allows these probabilities to evolve freely and independently over time. Simulation of population evolution with AEGIS demonstrates that ageing-like phenotypes evolve in stable environments under a wide range of conditions, that life history trajectories depend heavily on mutation rates, and that sexual populations are better able to accumulate high levels of beneficial mutations affecting early-life survival and reproduction. AEGIS is free and open-source, and aims to become a standard reference tool in the study of life-history evolution and the evolutionary biology of ageing.
A novel inhibitor of complement C5 provides structural insights into activation
Authors: Reichhardt Martin P. , Johnson Steven , Tang Terence , Morgan Thomas , Tebeka Nchimunya , Popitsch Niko , Deme Justin C. , Jore Matthijs M. , Lea Susan M.
Published: May 2019

The complement system is a crucial part of innate immune defences against invading pathogens. The blood-meal of thetick Rhipicephalus pulchelluslasts for days, and the tick must therefore rely on inhibitors to counter complement activation. We have identified a novel class of inhibitors from tick saliva, the CirpT family, and generated detailed structural data revealing their mechanism of action. We show direct binding of a CirpT to complement C5 and have determined the structure of the C5-CirpT complex by cryo-electron microscopy. This reveals an interaction with the peripheral macro globulin domain 4 (C5_MG4) of C5. To achieve higher resolution detail, the structure of the C5_MG4-CirpT complex was solved by X-ray crystallography (at 2.7 Å). We thus present the novel fold of the CirpT protein family, and provide detailed mechanistic insights into its inhibitory function. Analysis of the binding interface reveals a novel mechanism of C5 inhibition, and provides information to expand our biological understanding of the activation of C5, and thus the terminal complement pathway.
Phenotypic and genotypic consequences of CRISPR/Cas9 editing of the replication origins in the rDNA of Saccharomyces cerevisiae
Authors: Sanchez Joseph C. , Ollodart Anja , Large Christopher R. L. , Clough Courtnee , Alvino Gina M. , Tsuchiya Mitsuhiro , Crane Matthew , Kwan Elizabeth X. , Kaeberlein Matt , Dunham Maitreya J. , Raghuraman M. K. , Brewer Bonita J.
Published: May 2019

The complex structure and repetitive nature of eukaryotic ribosomal DNA (rDNA) is a challenge for genome assembly, and thus, the consequences of sequence variation in rDNA remain unexplored. However, renewed interest in the role that rDNA variation may play in diverse cellular functions, aside from ribosome production, highlights the need for a method that would permit genetic manipulation of the rDNA. Here, we describe a CRISPR/Cas9 based strategy to edit the rDNA locus in the budding yeast Saccharomyces cerevisiae. Using this approach, we modified the endogenous rDNA origin of replication in each repeat by deleting or replacing its consensus sequence. We characterized the transformants that have successfully modified their rDNA locus and propose a mechanism for how CRISPR/Cas9 mediated editing of the rDNA occurs. In addition, we carried out extended growth and life span experiments to investigate the long-term consequences that altering the rDNA origin of replication has on cellular health. We find that long-term growth of the edited clones results in faster growing suppressors that have acquired segmental aneusomy of the rDNA containing region of chr XII or aneuploidy of chromosomes XII, II, or IV. Furthermore, we find that all edited isolates suffer a reduced life span, irrespective of their levels of extrachromosomal rDNA circles. Our work demonstrates that it is possible to quickly, efficiently and homogeneously edit the rDNA locus via CRISPR/Cas9. It serves as a model for modifying other parts of the rDNA and, more generally, for editing other tandemly repeated sequences in higher eukaryotes.
The Firre locus produces a trans-acting RNA molecule that functions in hematopoiesis
Authors: Lewandowski Jordan P. , Lee James C. , Hwang Taeyoung , Sunwoo Hongjae , Goldstein Jill M. , Groff Abigail F. , Chang Nydia , Mallard William , Williams Adam , Henao-Meija Jorge , Flavell Richard A. , Lee Jeannie T. , Gerhardinger Chiara , Wagers Amy J. , Rinn John L.
Published: May 2019

RNA has been classically known to play central roles in biology, including maintaining telomeres1, protein synthesis2, and in sex chromosome compensation in certain species3,4. At the center of these important biological systems are noncoding RNAs. While thousands of long noncoding RNAs (lncRNAs) have been identified in mammalian genomes5–8, attributing RNA-based roles to lncRNA loci requires an assessment of whether the observed effect could be due to DNA regulatory elements, the act of transcription, or the lncRNA transcript. Here, we use the syntenically conserved lncRNA locus, Functional intergenic repeating RNA element (Firre), that is located on the X chromosome as a model to discriminate between DNA- and RNA-mediated effects in vivo. To this end, we generated genetically defined loss-of-function, gain-of-function, and rescue mouse models for Firre and provide genetic evidence that the Firre locus produces a trans-acting RNA. We report that: (i) Firre mutant mice have cell-specific defects during hematopoiesis and changes in gene expression that can be rescued by induction of Firre RNA from a transgene in the Firre knockout background, (ii) mice overexpressing Firre from a transgene exhibit increased levels of pro-inflammatory cytokines and impaired survival upon exposure to lipopolysaccharide, and (iii) deletion of the Firre locus did not result in changes in local gene expression on the X chromosome in 9 different biological contexts, suggesting that Firre does not function by cis-acting RNA or DNA elements. Together, our results provide genetic evidence that the Firre locus produces a trans-acting lncRNA that has physiological roles in hematopoiesis and immune function.
Cis-regulatory basis of sister cell type divergence in the vertebrate retina
Authors: Murphy Daniel , Hughes Andrew. E.O. , Lawrence Karen A. , Myers Connie A. , Corbo Joseph C.
Published: May 2019

Multicellular organisms evolved via repeated functional divergence of transcriptionally related sister cell types, but the mechanisms underlying sister cell type divergence are not well understood. Here, we study a canonical pair of sister cell types, retinal photoreceptors and bipolar cells, to identify the key cis-regulatory features that distinguish them. By comparing open chromatin maps and transcriptomic profiles, we found that while photoreceptor and bipolar cells have divergent transcriptomes, they share remarkably similar cis-regulatory grammars, marked by enrichment of K50 homeodomain binding sites. However, cell class-specific enhancers are distinguished by enrichment of E-box motifs in bipolar cells, and Q50 homeodomain motifs in photoreceptors. We show that converting K50 motifs to Q50 motifs represses reporter expression in bipolar cells, while photoreceptor expression is maintained. These findings suggest that partitioning of Q50 motifs within cell type-specific cis-regulatory elements was a critical step in the divergence of the bipolar transcriptome from that of photoreceptors.
The Prevalence and Patterns of Combined Psychotropic Polypharmacy among Acute Care Hospitals in Japan
Authors: Shimizu Sayuri , Okumura Yasuyuki , Ishikawa Koichi B. , Matsuda Shinya , Ito Hiroto , Fushimi Kiyohide
Published: May 2019

Purpose

To evaluate the prescribing patterns of psychotropic polypharmacy for inpatients of acute care hospitals in Japan.

Methods

Administrative data on 2,639,885 patients admitted to acute care hospitals in Japan between July and December of 2008 were analyzed retrospectively. We defined psychotropic medications as antipsychotics, antidepressants, benzodiazepines, and other sedatives/hypnotics and studied their prescription patterns during the hospitalization of patients with stroke, acute cardiac infarction, cancer, and diabetes mellitus.

Results

At least one psychotropic drug was prescribed in 35.9% of all cases. Two-drug combinations of antipsychotic drugs were prescribed for stroke patients in 14,615 cases (1.4%), more than 2 in 3,132 cases (0.3%), and 22.4% of cases were prescribed 2 or more psychotropic drugs in addition to antipsychotic drugs. Amongst upper gastrointestinal cancer patients, 7.7% were prescribed a combination of 2 or more drugs, including benzodiazepines. Of the upper gastrointestinal cancer patients who were prescribed benzodiazepines, 20.3% were also prescribed 2 or more psychotropic drugs. Amongst stroke and upper gastrointestinal cancer patients, 36.6% and 35.6%, respectively, were treated with combination therapy using drugs of this class and others.

Conclusion

There is a pattern of polypharmacy that combines benzodiazepines and other sedatives/hypnotics with antidepressants or antipsychotic drugs, and this study provides a detailed analysis of this within acute care hospitals. Our results indicate the need for additional research into the efficacy of polypharmacy for inpatients in non-psychiatric settings.
Transcriptional bursts explain autosomal random monoallelic expression and affect allelic imbalance
Authors: Larsson Anton J.M. , Reinius Björn , Jacob Tina , Dalessandri Tim , Hendriks Gert-Jan , Kasper Maria , Sandberg Rickard
Published: May 2019

Transcriptional bursts render substantial biological noise in cellular transcriptomes. Here, we investigated the theoretical extent of monoallelic expression resulting from transcriptional bursting and how it compared to the amounts of monoallelic expression of autosomal genes observed in single-cell RNA-sequencing (scRNA-seq) data. We found that transcriptional bursting can explain frequent observations of autosomal monoallelic gene expression in cells. Importantly, the burst frequency largely determined the fraction of cells with monoallelic expression, whereas both burst frequency and size contributed to allelic imbalance. Allelic observations deviate from the expected when analysed across heterogeneous groups of cells, suggesting that allelic modelling can provide an unbiased assessment of heterogeneity within cells. Finally, large numbers of cells are required for analyses of allelic imbalance to avoid confounding observations from transcriptional bursting. Altogether, our results shed light on the implications of transcriptional burst kinetics on allelic expression patterns and phenotypic variation between cells.
Crystal structure of methyl α-L-rhamnopyranosyl-(1→2)-α-L-rhamnopyranoside monohydrate
Authors: Eriksson Lars , Widmalm Göran
Published: May 2019

The title compound, C13H24O9·H2O, a structural model for part of bacterial O-antigen polysaccharides from Shigella flexneri and Escherichia coli, crystallizes with four independent disaccharide molecules and four water molecules in the asymmetric unit. The conformation at the glycosidic linkage joining the two rhamnosyl residues is described by the torsion angles φH of 39, 30, 37 and 37°, and ψH of −32, −35, −31 and −32°, which are the major conformation region known to be populated in an aqueous solution. The hexopyranose rings have the 1
C
4 chair conformation. In the crystal, the disaccharide and water molecules are associated through O—H...O hydrogen bonds, forming a layer parallel to the bc plane. The layers stack along the a axis via hydrophobic interactions between the methyl groups.
Regional tourism at the farmers’ market: consumers’ preferences for local food products
Authors: Garner Benjamin , Ayala Cesar
Published: May 2019

Purpose

The purpose of this paper is to examine farmers’ market consumer behavior through a regional food and culinary tourism lens to see the ways these festive and atmospheric markets can be used to develop a regional brand or identity surrounding food production.

Design/methodology/approach

This study was based on a survey of 270 participants in a farmers’ market in the USA. A combination of descriptive and statistical analyses was used to analyze consumer habits and spending.

Findings

The findings in this study suggest that while most of the customers live in a town where the market is located, a significant number of customers come from other locations, with some traveling significant distances, to participate in this market, particularly for the Saturday market. Many of the customers come to purchase organic and local foods.

Research limitations/implications

This work is limited, in that it is a case study at one farmers’ market in the USA, and the work is exploratory in nature.

Practical implications

This work has implications for market managers seeking to increase their consumer base. Markets that want to increase their reach would do well to promote their events to a wider geographic area. The results presented here showed that consumers are willing to drive upward of 40 miles to attend a high-quality market.

Originality/value

This work expands our conceptualization of farmers’ markets by suggesting that these markets have the potential to form the backbone of a region is food identity through the creation of a food destination.
The patterns of the numbers used in occupational fraud schemes
Authors: Nigrini Mark J.
Published: May 2019

Purpose

This study aims to classify the numbers used in recent financial statement, corruption and asset misappropriation fraud schemes in such a way that these classes can be used to design effective proactive analytics-based fraud detection tests.

Design/methodology/approach

The data sources for the classification scheme include the court records of fraud prosecutions, investigative reports and research papers related to fraud cases.

Findings

Fraudulent numbers are most often amounts that are round, have a strong period-over-period growth, are just above or below internal control thresholds or other targets, are deviations from Benford’s Law, are purposeful duplicates of authentic transactions, are outliers due to being excessively large and are excessively rounded up or down. The study includes several examples of fraudulent numbers.

Research limitations/implications

The fraudulent number types are based on a sample of fraud-related court documents, and the sample might not be representative of the population of detected and undetected frauds. Further research is needed into the detection of corruption/bribery schemes.

Practical implications

The results are important for auditors and forensic accountants running proactive fraud detection tests. The discussions emphasize that the analysis should include refining and rerunning the tests, and then using groupings and filtering to deal with false positives. The importance of an effective audit of the notable transactions is stressed in the concluding section.

Originality/value

The study is an original in-depth coverage of the patterns found in fraudulent numbers. The discussion sections review implementation issues and considerations for future research.
Optimism-pessimism effects on money demand: theory and evidence
Authors: Karpetis Christos , Papadamou Stephanos , Spyromitros Eleftherios , Varelas Erotokritos
Published: May 2019

Purpose

The purpose of this paper is to investigate, both theoretically and empirically, the relationship between optimism (pessimism) – as reflected by animal spirits – and money demand by taking into account transaction costs.

Design/methodology/approach

Inspired by the theoretical model of money demand by Teleset al.(2016) the authors incorporate the optimism (pessimism) effects in the money demand. Then, using the consumers’ confidence indicator as a proxy indicator of optimism/pessimism, they estimate the money demand in a panel data framework.

Findings

The theoretical framework suggests that the optimism (pessimism) effects on money demand are positive (negative). Empirical evidence for 11 Eurozone countries divided in two groups (i.e. core and periphery) confirms the theoretical considerations.

Practical implications

It appears that periphery countries with a higher sensitivity to the recent financial crisis present lower real money demand sensitivity to consumption expenditures and higher real money demand sensitivity to consumer confidence index. Moreover, in such countries, money demand changes present higher persistence over time. Thus, the authors observe differing attitudes concerning money demand across Eurozone citizens that should be taken into account by monetary policymakers (i.e. the ECB).

Originality/value

The authors introduce, in the vast literature on money demand, both theoretically and empirically the role of optimism (pessimism). Differences across core and periphery Eurozone countries identified.
Insider Information: The Ethicality of the High Frequency Trading Industry
Authors: Sobolev Daphne
Published: May 2019

This study explores the ethical perceptions of employees in the financial industry. Focusing on the high frequency trading (HFT) industry, it analyses a series of interviews with HFT employees (managers, computer programmers and traders). It shows that regulations and firm rules profoundly affect HFT practices. However, they do not provide employees with answers for their ethical questions. To judge the ethicality of HFT, employees choose reference stakeholder groups and assess the way HFT impacts them. The perception that HFT has a positive effect on stakeholder groups is associated with moral satisfaction, whereas the perception that it has a negative effect is related to emotional detachment, sense of meaninglessness and turnover intent. The high variance in employees’ choices of stakeholder reference groups emphasizes the subjectivity and uncertainty that HFT ethicality entails. Therefore, this study suggests that the financial industry may lack moral leadership. It makes empirical and theoretical contributions to the ‘business ethics as practice’ theory and examines management and regulatory applications.
Experiences of Urban Militarism: Spatial Stigma, Ruins and Everyday Life
Authors: Pasquetti Silvia
Published: May 2019

A key question in urban sociology is how people interpret the urban environment. At a time when cities are increasingly militarized, this question is particularly important for understanding how militarism impacts urban life. However, urban sociologists have not addressed how people experience militarized environments. This article turns to this question by considering the case of Lydda‐Lod, an Israeli city that has been demographically and physically transformed by war, displacement and securitization. Drawing on Wacquant's sociology of spatial stigma and adding insights from works on emotions in (post‐)conflict cities, I examine how poor Palestinians think and feel about the surveilled districts where they live within the city's broader landscape of ruins. I show how the Israeli military, security and policing agencies have collectively produced spatial stigmatization of these districts. I discuss how Palestinians respond to this spatial stigma by attaching a sense of worthlessness to their districts. However, this reproduction of spatial stigma is punctuated by expressions of care for the built environment and by a desire to revalorize collective Palestinian life in the city. I conclude by discussing how a perspective on militarized cities focused on everyday responses to militarism and attentive to marginalities enriches urban sociology and urban studies more generally.
Complexation of Amylosucrase‐Modified Waxy Corn Starch with Fatty Acids: Determination of Their Physicochemical Properties and Digestibilities
Authors: Lim Joo Hee , Kim Ha Ram , Choi Seung Jun , Park Cheon‐Seok , Moon Tae Wha
Published: May 2019

In this study, starch–lipid complexes were prepared using normal corn starch (NC) and amylosucrase‐modified waxy corn starch (ASWC) with myristic acid (C14:0) and palmitic acid (C16:0). The amylosucrase modification elongated branch chains in waxy corn starch leading to an increase of apparent amylose content (29.7%) similar to that of NC (29.0%). The X‐ray diffraction of starch–lipid complexes revealed a V‐type pattern, a clear indication of complex formation. The ability of the ASWC to complex with fatty acids was greater than that of NC. Interestingly, the changes in relative crystallinity, thermal parameters, and digestion properties according to the complexation showed opposite patterns in NC and ASWC. This study found that the structure of ASWC contributes to the formation of starch–fatty acid complexes and suggested that the ASWC can be preferred over NC in a delivery system.

Practical Application

Amylopectin has been considered to be incapable of forming complexes with fatty acids due to its short chain length and steric hindrance. Through this study, an appropriate enzymatic modification of the molecular structures of waxy starches could make a complexation of waxy starches with fatty acids possible. The findings of this study suggest a promising perspective for utilization of waxy starch as a carrier material of lipophilic molecules.
phenotools: An r package for visualizing and analysing phenomic datasets
Authors: Eliason Chad M. , Edwards Scott V. , Clarke Julia A.
Published: May 2019

Phenotypic data are crucial for understanding genotype–phenotype relationships, assessing the tree of life and revealing trends in trait diversity over time. Large‐scale description of whole organisms for quantitative analyses (phenomics) presents several challenges, and technological advances in the collection of genomic data outpace those for phenomic data. Reasons for this disparity include the time‐consuming and expensive nature of collecting discrete phenotypic data and mining previously published data on a given species (both often requiring anatomical expertise across taxa), and computational challenges involved with analysing high‐dimensional datasets.

One approach to building approximations of organismal phenomes is to combine published datasets of discrete characters assembled for phylogenetic analyses into a phenomic dataset. Despite a wealth of legacy datasets in the literature for many groups, relatively few methods exist for automating the assembly, analysis, and visualization of phenomic datasets in phylogenetic contexts. Here, we introduce a new r package phenotools for integrating (fusing original or legacy datasets), curating (finding and removing duplicates) and visualizing phenomic datasets.

We demonstrate the utility of the proposed toolkit with a morphological dataset for flightless birds and two morphological datasets for theropod dinosaurs and provide recommendations for character construction to maximize accessibility in future workflows. Visualization tools allow rapid identification of anatomical subregions with difficult or problematic histories of homology.

We anticipate these tools aiding automation of the assembly and visualization of phenomic datasets to inform evolutionary relationships and rates of phenotypic evolution.
Cannabis Use Disorder and Epilepsy: A Cross‐National Analysis of 657 072 Hospitalized Patients
Authors: Patel Rikinkumar S. , Mekala Hema M. , Tankersley William E.
Published: May 2019

Background and Objectives

Recent evidence has suggested that cannabis use precipitates cerebrovascular events. We investigated the relationship between cannabis use disorder (CUD) and hospitalization for epilepsy.

Methods

Nationwide inpatient sample (NIS) was analyzed from 2010 to 2014 for patients (age 15‐54) with a primary diagnosis of epilepsy (N = 657 072) and comparison was made between patients with ICD‐9 classification of CUD and without CUD. We utilized logistic regression to study the association (odds ratio [OR]) between CUD and epilepsy.

Results

The incidence of CUD in epilepsy patients was 5.77%, and patients with CUD had a threefold higher likelihood of emergency admissions. Patients with CUD were younger (25‐34 years), male and African American. In regression analysis, adjusted for confounders, cannabis (OR, 1.56), tobacco (OR, 1.20), and alcohol (OR, 1.63) use disorders were found to be associated with higher odds of epilepsy hospitalization, but lower odds with cocaine (OR, 0.953), amphetamine (OR, 0.893), and opioid (OR, 0.828) use disorders.

Conclusions and Scientific Significance

With the increasing prevalence of medical marijuana legalization, there is increased use of medicinal marijuana. Studies of cannabidiol and marijuana for epilepsy have been highly publicized, leading to its off‐label use for treatment. There is limited evidence to suggest that the cannabinoids may also induce a seizure. This study found that CUD is independently associated with a 56% increased likelihood of epilepsy hospitalization and this association persists even after adjusting for other substance use disorders and confounders. (Am J Addict 2019;28:353–360)
Determination of the minimally important difference in a nasal symptom score in house dust mite allergy
Authors: Devillier Philippe , Brüning Harald , Bergmann Karl‐Christian
Published: May 2019

Background

House dust mite (HDM) allergens are responsible for the most prevalent persistent respiratory allergies. Clinical trials in this field often use a four‐component nasal symptom score (T4NSS) as a measure of efficacy.

Methods

The present observational, prospective, multinational, multicenter study determined the minimal important difference (MID) for a T4NSS in children, adolescents, and adults with physician‐diagnosed HDM‐induced allergic rhinoconjunctivitis (AR). Patients rated the T4NSS daily, a 15‐point global rating of change scale (GRCS) and the Rhinoconjunctivitis Quality of Life Questionnaire weekly. The MID was determined primarily by using a regression method with a GRCS threshold of 2.

Results

A total of 546 patients (210 adults, 133 adolescents, and 203 children) were included; 92.6% of the patients had moderate‐to‐severe AR, and 30.1% had concomitant mild asthma. During the first week, the mean ± standard deviation T4NSS was 5.68 ± 2.76 in adults, 5.34 ± 2.66 in adolescents, and 5.07 ± 2.48 in children. In a GRCS regression analysis, the MID [95% confidence interval] for the T4NSS was −0.90 [−1.06;‐0.75] overall (n = 509), −0.94 [−1.19;‐0.69] in children (n = 187), −0.74 [−1.07;‐0.41] in adolescents (n = 125), and −1.04 [−1.29;‐0.79] in adults (n = 197). The MID did not differ greatly from one disease severity tertile to another. Confirmatory distribution‐based analyses yielded overall MID values of −0.87 for the first week of the study and −0.93 for the week 2–week 1 difference.

Conclusion

The MID for improvement in the T4NSS is at least −0.90 units in children, adolescents, and adults suffering from HDM‐induced AR This value could be rounded up to −1 unit for convenience.
The Life of Winds: Knowing the Namibian Weather from Someplace and from Noplace
Authors: Schnegg Michael
Published: May 2019

This article brings the two questions, how and what we know, into a productive dialog to explain the difference between indigenous and scientific environmental knowledge. In the case I explore, scientists and Damara pastoralists (ǂnūkhoen) both relate the arrival of the rains in arid Namibia to the interplay between two winds. However, when it comes to explaining those observations, their accounts could hardly be more different. While Indigenous people understand the arrival of the rains as a play between loving and caring winds, scientists recognize them as a consequence of a shift of the Intertropical Convergence Zone. Building on Heidegger's phenomenology, I explore the relationship between the knower and the known. My main theoretical intervention is to show that Damara people and scientists have distinct ways of encountering the world: from someplace and from noplace. In those encounters, the weather is either enmeshed in forms of use in everyday skilled activity for rural pastoralists, or enframed by technology for scientists. By encountering the weather from someplace and from noplace, the world turns into a different place for each. The engagement with these weather worlds shows how ways of knowing the environment can be multiple, but they are not mutually exclusive. [Indigenous knowledge, weather, phenomenology, ontology, Heidegger]
Vitamin A levels are comparable between children with newly diagnosed coeliac disease and non‐coeliac controls
Authors: Weintraub Yael , Ben‐Tov Amir , Dotan Gad , Yerushalmy‐Feler Anat , Weiner Dror , Levy Dina , Lubetzky Ronit , Cohen Shlomi
Published: May 2019

Aim

Nutritional deficiencies associated with coeliac disease include iron, folic acid and fat‐soluble vitamins. This study compared the prevalence and degree of vitamin A deficiency among newly diagnosed coeliac disease patients to controls in a developed country.

Methods

This prospective cohort study included all children evaluated by gastroscopy at Dana‐Dwek Children's Hospital, Israel, between September 2014 and February 2017. Vitamin A, haemoglobin, C‐reactive protein (CRP), ferritin, tissue transglutaminase, immunoglobulin A and vitamin D levels were measured.

Results

Of the 113 children (69% females), 47 were diagnosed with coeliac disease whereas the others were the controls (mean age of 8.2 ± 3.8 years and 12.4 ± 3.5 years, respectively). There was no group difference in vitamin A, vitamin D or CRP levels. Among coeliac children, two had true vitamin A deficiency compared with three controls, while 18 coeliac children had subclinical vitamin A deficiency compared with 25 controls (p > 0.05).

Conclusion

Paediatric coeliac disease was not associated with increased prevalence of vitamin A deficiency. Children evaluated for gastrointestinal complaints in a developed country were found to have an unexpectedly high prevalence of subclinical vitamin A deficiency. Further prevalence and causality assessments of vitamin A deficiency in developed countries are needed.
Thalassaemia intermedia caused by coinheritance of a β‐thalassaemia mutation and a de novo duplication of α‐globin genes in the paternal allele
Authors: Pang Dejian , Shang Xuan , Cai Decheng , Zhu Fei , Cheng Yi , Zhong Jianmei , Yi Sheng , Zhang Qianqian , Xu Xiangmin
Published: May 2019

Next generation sequencing identified a de novo, 204 kb, tandem duplication (αααα204) in the α‐globin gene cluster of a Chinese thalassaemia intermedia patient. Haplotype analysis showed that the duplicated chromosome was of paternal origin. Molecular analysis of genomic DNA from the patient's lymphocytes, hair follicles, buccal mucosa cells, his father's lymphocytes and sperm cells excluded the possibility of somatic or germinal mosaicism. The analysis also indicated that this duplication arose during spermatogenesis. The microhomology in the breakpoint was found and suggested that this duplication could be formed by a coupled homologous and non‐homologous recombination mechanism.
Longitudinal sequencing of RUNX1 familial platelet disorder: new insights into genetic mechanisms of transformation to myeloid malignancies
Authors: Duarte Bruno K. L. , Yamaguti‐Hayakawa Gabriela G. , Medina Samuel S. , Siqueira Lúcia H. , Snetsinger Brooke , Costa Fernando F. , Rauh Michael J. , Ozelo Margareth C.
Published: May 2019

The mechanisms by which patients with RUNX1 familial platelet disorder with propensity to myeloid malignancies (FPDMM) develop myeloid malignancies (MM) are not fully understood. We report the results of targeted next‐generation sequencing on three patients with RUNX1 FPDMM who developed acute myeloid leukaemia or myelodysplastic syndromes (AML/MDS). DNA samples were collected from bone marrow, peripheral blood and buccal swabs at different time points. One patient had clonal haematopoiesis, represented by an SRSF2 p.P95R variant, prior to his AML diagnosis, when he developed an additional NRAS p.G12D variant. His sister presented to us with MDS, with a TET2 p.S471fs and identical NRAS p.G12D variant. The third patient, from another family, had an additional RUNX1 p.R204X and an NFE2 p.Q139fs variant at AML diagnosis. This constitutes the first report of NFE2 variants in AML without extramedullary disease and NRAS variants in AML/MDS in the setting of FPDMM. A systematic review of the literature including our findings distinguishes two genetic landscapes at AML transformation from FPDMM characterized by either the presence or absence of somatic abnormalities in RUNX1 with or without variants in genes usually associated with MM. Whether clonal haematopoiesis precedes transformation only in patients without somatic abnormalities in RUNX1 needs further confirmation.
Trends in biodiversity and habitat quantification tools used for market‐based conservation in the United States
Authors: Chiavacci Scott J. , Pindilli Emily J.
Published: May 2019

Market‐based conservation mechanisms are designed to facilitate the mitigation of harm to and conservation of habitats and biodiversity. Their potential is partly hindered, however, by the quantification tools used to assess habitat quality and functionality. Of specific concern are the lack of transparency and standardization in tool development and gaps in tool availability. To address these issues, we collected information via internet and literature searchers and through conversations with tool developers and users on tools used in U.S. conservation mechanisms, such as payments for ecosystem services (PES) and ecolabel programs, conservation banking, and habitat exchanges. We summarized information about tools and explored trends among and within mechanisms based on criteria detailing geographic, ecological, and technical features of tools. We identified 69 tools that assessed at least 34 species and 39 habitat types. Where tools reported pricing, 98% were freely available. More tools were applied to states along the U.S. West Coast than elsewhere, and the level of tool transferability varied markedly among mechanisms. Tools most often incorporated conditions at numerous spatial scales, frequently addressed multiple risks to site viability, and required 1–83 data inputs. Most tools required a moderate or greater level of user skill. Average tool‐complexity estimates were similar among all mechanisms except PES programs. Our results illustrate the diversity among tools in their ecological features, data needs, and geographic application, supporting concerns about a lack of standardization. However, consistency among tools in user skill requirements, incorporation of multiple spatial scales, and complexity highlight important commonalities that could serve as a starting point for establishing more standardized tool development and feature‐incorporation processes. Greater standardization in tool design may expand market participation and facilitate a needed assessment of the effectiveness of market‐based conservation.
Acute and chronic pain in orofacial trauma patients
Authors: Khan Junad , Zusman Tal , Wang Qian , Eliav Eli
Published: May 2019

Trauma or injury to the dentition and supporting tissues is associated with pain and discomfort, as expected, that may present immediately, shortly afterwards, or within a few days. Pain is an essential response to injury because it allows the organism to develop avoidance behavior to potential threats and helps the organism to avoid usage of the injured organ during the healing process. Not only does external trauma induce pain, but also essential invasive dental procedures such as extractions, dental implant insertions, root canal treatments, and oral surgeries are accompanied by similar post‐surgical (post‐traumatic) pain. The pain intensity after trauma varies and does not always correlate with the extent of injury. Trauma to the orofacial region or the teeth may also indirectly affect and induce pain in other orofacial structures such as the masticatory muscles, the temporomandibular joint, and even the cervical spine. In most cases, the pain will resolve as soon as healing of the affected tissue occurs or after dental and routine palliative treatment. In a limited number of cases, the pain persists beyond healing and evolves into a chronic pain state. Chronic pain in the orofacial region presents diagnostic and management challenges. Misdiagnosis or delayed diagnosis of the oral chronic pain condition may lead to unnecessary dental treatment. This article will discuss diagnosis and treatment for acute and chronic pain as well as potential mechanisms involved in the undesirable transition from acute to chronic pain.
Microbiological aspects of traumatic injuries
Authors: Fouad Ashraf F.
Published: May 2019

After traumatic injuries to teeth, microorganisms may invade the compromised pulp tissue and initiate pulp infection and periapical inflammation. In addition to bone resorption that typically accompanies pulp necrosis, root resorption frequently occurs. Root resorption has several variants that may occur shortly after the trauma or at a later stage. The pathological changes seen after traumatic injuries to teeth are invariably linked to the presence of microbial irritants. The presence of bacterial biofilms in the dental pulp space can be treated with regenerative or therapeutic endodontic procedures. However, necrosis of periodontal ligament is usually terminal for the tooth involved. In this review, the sources of bacteria after traumatic injuries are discussed. The types and role of microorganisms involved in the pathogenesis of endodontic pathosis after traumatic injuries are presented, and contemporary approaches for the management of these conditions are reviewed. Contemporary antimicrobial strategies are discussed. The rationale for the use of systemic and topical antimicrobials is presented. Finally, novel approaches to the use of antimicrobial therapies, particularly in regenerative procedures, are reviewed.
Long‐acting antipsychotic medication as first‐line treatment of first‐episode psychosis with comorbid substance use disorder
Authors: Abdel‐Baki Amal , Thibault Dominic , Medrano Sofia , Stip Emmanuel , Ladouceur Martin , Tahir Ramzan , Potvin Stephane
Published: May 2019

Aim

Substance use disorder (SUD) is highly prevalent among patients with first‐episode psychosis (FEP) and associated with poor adherence and worst treatment outcomes. Although relapses are frequent in FEP, current literature on long‐acting injectable antipsychotics (LAI‐AP) use in FEP is scarce and studies often exclude patients with SUD.

Objectives

To determine the impact of LAI‐AP as first‐line treatment on psychotic relapses or rehospitalizations in FEP patients with comorbid SUD (FEP‐SUD).

Methods

This is a naturalistic, longitudinal, 3‐year prospective and retrospective study on 237 FEP‐SUD admitted in two EIS in Montreal, between 2005 and 2012. The patients were divided on the basis of first‐line medication introduced, either oral antipsychotics (OAP, n = 206) or LAI‐AP (n = 31). Baseline characteristics were compared using χ² test and analysis of variance, and Kaplan‐Meier survival analysis was performed on relapse and rehospitalization.

Results

Compared to the OAP group, patients in the LAI‐AP group presented worse prognostic factors (eg, history of homelessness). Despite this, the LAI‐AP group presented a lower relapse rate (67.7% vs 76.7%), higher relapse‐free survival time (694 vs 447 days, P = 0.008 in Kaplan‐Meier analysis), and trends for reduced rehospitalization rates (48.4% vs 57.3%) and hospitalization‐free survival time (813 vs 619 days, P = 0.065 Kaplan‐Meier analysis). Of those receiving OAP as first‐line, 41.3% were eventually switched to LAI‐AP and displayed worst outcome in relapse and rehospitalization.

Conclusion

LAI‐AP should be strongly considered as first‐line treatment of FEP‐SUD patients since this pharmacological option reduces the risk of relapse and rehospitalization even in the individuals with poor prognostic factors.
Atraumatic vs conventional restorative treatment for root caries lesions in older patients: Meta‐ and trial sequential analysis
Authors: Göstemeyer Gerd , da Mata Cristiane , McKenna Gerald , Schwendicke Falk
Published: May 2019

Objectives

We aimed to appraise the comparative clinical efficacy of atraumatic restorative treatment (ART) versus conventional restorative treatment (CT) using a meta‐analysis, and assessed the robustness of evidence by trial sequential analysis (TSA).

Background

Due to its simplified clinical approach, ART may be advantageous over CT for restoration of root caries lesions in institutionalised older patients.

Methods

Three electronic databases (PubMed, Embase and Cochrane CENTRAL) were screened, and hand searches and cross‐referencing performed to identify randomised controlled trials reporting on survival of ART vs CT for restoration of root caries in older patients. Trial selection, data extraction and risk of bias assessment were performed by two independent reviewers. ART and CT were compared using fixed‐ or random‐effects pairwise meta‐analysis for per‐protocol (PP), intention‐to‐treat (ITT) and best‐case scenarios. TSA was used to control for risk of random errors.

Results

A total of 235 studies were identified, and three trials involving 130 patients (463 restorations) were included. Risk of bias was high or moderate in all but one trial. ART was associated with a significantly increased risk of failure (OR [95% CI] 2.06 [1.06/4.00]) in PP‐ but not in ITT analysis (1.36 [0.92/2.02]). Analyses for best‐case scenarios found great uncertainty introduced by attrition. No firm evidence was reached according to TSA.

Conclusions

For restoration of root caries, there is insufficient data to clearly rule out whether differences between ART and CT exist. Limited available data indicate there might be an increased risk of failure for ART.
Mirror meetings with frail older people and multidisciplinary primary care teams: Process and impact analysis
Authors: Grol Sietske , Molleman Gerard , Schers Henk
Published: May 2019

Objectives

To analyse the process and impact of confronting multidisciplinary teams (MTs) in primary care with the experiences of frail older patients through mirror meetings (MMs), with the aim of supporting teams to organize care in a more patient‐oriented way.

Methods

Process and impact analyses were performed using a mixed‐method approach. MMs were held with 14 frail older patients and four MTs comprising 23 health‐care professionals (HCPs) in primary care in the Netherlands.

Results

Mirror meetings were feasible for frail older people living at home, although their recruitment was time‐consuming. Interaction between the patients was scarce, but they valued the opportunity to share their stories. HCPs preferred MMs overwritten reports about patient experiences. An impact analysis revealed four dominant professional areas for improvement: improve alignment with patient goals, improved communication with patients both orally and in writing, developing new pathways to connect with informal caregivers and an increased understanding that most HCPs are relative strangers to their patients.

Conclusions

Mirror meetings are a relatively simple and promising method for exploring the ways in which frail older patients experience care.

Practice implications

Given the right conditions, MMs could result in valuable processes to enable MTs to improve their working methods.
Aleurone cells are the primary contributor to arabinoxylan oligosaccharide production from wheat bran after treatment with cell wall‐degrading enzymes
Authors: Vangsøe Cecilie Toft , Sørensen Jens Frisbæk , Bach Knudsen Knud Erik
Published: May 2019

Arabinoxylans and in particular arabinoxylan oligosaccharides (AXOS) from wheat are recognised for their prebiotic potential. A high‐yield, non‐chemical production of AXOS is therefore of interest when producing functional foods. This study investigated the enzymatic production of AXOS from wheat bran with the aim of establishing the main fraction contributing to production of AXOS. Fractions of wheat bran, outer pericarp and aleurone with two different purities were treated with the cell wall‐degrading enzymes: xylanase, cellulase and β‐glucanase. The yield of solubilised arabinoxylans upon treatment was greatest in the most pure aleurone fraction (164 g kg−1) and lowest in the outer pericarp fraction (15 g kg−1). The yield was mainly recovered as AXOS rather than soluble arabinoxylans and was negatively related to the arabinose/xylose ratio found in the raw material. In conclusion, wheat aleurone cell walls are the main contributor to the production of AXOS from wheat bran and this seems to depend on the A/X ratio of the raw material.