bluuebunny/crossref_metadata_2025 huggingface dataset:
Ectopic HOTTIP Expression Induces Non-canonical Transactivation Pathways to Promote Growth and Invasiveness in Pancreatic Ductal Adenocarcinoma
Authors: Wong Chi Hin , Li Chi Han , He Qifang , Lam Chan Stephen , Tong Joanna Hung-Man , To Ka-Fai , Chen Yangchao
Published: October 2019

LncRNA HOTTIP (HOXA transcript at the distal tip) is upregulated in pancreatic ductal adenocarcinoma (PDAC). However, oncogenic pathway mediated by HOTTIP is not fully understood. We identified canonical HOTTIP-HOXA13 targets: CYP26B1, CLIC5, CHI3L1 and UCP2 which were responsible for cell growth and cell invasion. Importantly, genome-wide analysis revealed that 38% of the genes regulated by HOTTIP contained H3K4me3 and HOTTIP enrichment at their promoters, without HOXA13 binding. HOTTIP complexed with WDR5-MLL1 totrans-activate oncogenic proteins CYB5R2, SULT1A1, KIF26A, SLC1A4 and TSC22D1 through directly triggering H3K4me3 at their promoters. The WDR5, MLL1 and H3K4me3 levels at their promoters and their expression levels were sensitive to HOTTIP overexpression and knockdown. These suggested the importance of non-canonicaltrans-acting HOTTIP-WDR5-MLL1 pathway in HOTTIP-regulatory mechanism by promoting the expression of oncogenic proteins. Furthermore, we dissected the mechanism by which HOTTIP was regulated by miR-497 in PDAC. Analysis of PDAC human tissues also revealed that HOTTIP was negatively correlated with miR-497 level. Our findings demonstrated that HOTTIP, upregulated in PDAC due to the loss of inhibitory miR-497, promoted PDAC progression through canonical HOTTIP-HOXA13 axis and a novel non-canonicaltrans-acting HOTTIP-WDR5-MLL1-H3K4me3 pathway.
The abstract space and the alienation of political public space in the Middle East
Authors: Zamani Farzad , Mehan Asma
Published: October 2019

Purpose

The purpose of this paper is to explain how abstract space of the State – universally and specifically within the context of Middle Eastern cities – aims to homogenise the city and eliminate any anomaly that threatens its power structure.

Design/methodology/approach

Through a historical and discourse analysis of these policies and processes in the two case studies, this paper presents a contextualised reading of Lefebvre’s concept of abstract space and process of abstraction in relation to the alienation of political public spaces.

Findings

The paper proposes that regardless of these homogenising strategies being applied universally, they fail to respond to contextual particularities and therefore they – in a contradictory manner – may themselves produce a space of resistance and difference.

Originality/value

This paper focusses on Iran, the case of Tehran and Turkey, the case of Taksim Square and Gezi Park in Istanbul. Recent policies and strategies have been proposed and implemented to reduce, alienate and possibly neutralise the impacts of urban and political protests in these cities and socio-political contexts.
Food traceability technologies and foodborne outbreak occurrences
Authors: Magalhães Ana Elisa Vianna , Rossi Arthur Henrique Gomes , Zattar Izabel Cristina , Marques Marcos Augusto Mendes , Seleme Robson
Published: October 2019

Purpose

The purpose of this paper is to identify the relationship between the frequency of publication on food supply chain (FSC) traceability and the occurrence of foodborne diseases outbreaks.

Design/methodology/approach

A systematic review of the literature was carried out to locate the main articles published in the literature, followed by a content analysis in order to list the main food traceability technologies and their evolutions. Finally, a Spearman’s ρ correlation analysis between the frequency of publications on FSC traceability and the annual occurrence of foodborne outbreaks in the five largest food exporting countries in the world was performed.

Findings

In these analyses, the tools of radiofrequency, deoxyribonucleic acid, wireless sensor network, hazard analysis and critical control points and Internet of Things are the most researched technologies, and they are relevant in the evolution of traceability in the FSC. With correlation coefficients above 0.700 at 0.01 significance levels, this evolution of food traceability technologies has been one of the factors reducing the number of food outbreaks in the USA and Germany, countries with greater development of the health system and food control.

Originality/value

This paper provides an evaluation of the food traceability technologies and the effects of their evolutions in the occurrence of food outbreaks. This may help in the proposal of public policies related to food and outbreak control.
Processed food choice based on the theory of planned behavior in the context of nutritional warning labels
Authors: Aliaga-Ortega Luis , Adasme-Berríos Cristian , Méndez Caren , Soto Carolina , Schnettler Berta
Published: October 2019

Purpose

The purpose of this paper is to analyze the effect of nutritional warning (NW) labels on the behavior of consumers of processed foods, considering demographic and psychological factors associated with the theory of planned behavior (TPB).

Design/methodology/approach

The study had a descriptive and cross-sectional design. A survey was applied to 200 household food decision makers from central Chile. This questionnaire was developed based on the planned behavior theory that evaluates the psychological constructs of human behavior: Attitude (ATT), Subjective Norms (SN), Perceived Behavioral Control (PBC) and Purchase Intention (PI) toward processed foods with NW. Sociodemographic variables were also included. The data were analyzed by using a multinomial logit (MNL) model, where three types of categories are established depending on the choice made by the consumer. Thus, the dependent variable responds to the effect of the following probabilities: Eliminate from Consumption, Do Not Eliminate from Consumption and Do Not Know whether or not to eliminate from consumption when selecting a food processed with NW.

Findings

The results show that the implementation of NW has significant effects on the choice of processed foods purchases made by Chilean consumers. Consumers with negative ATT and PBC in the presence of NW on processed foods eliminated this type of food from their consumption. On the other hand, those who did not eliminate processed foods with NW from their consumption made that choice because they had a positive PBC. In addition, consumers who were unsure about eliminating or consuming processed foods with NW also had a positive PBC. In addition, SN and sociodemographic variables did not affect consumer choice.

Practical implications

The results of this study are crucial in informing public policy strategies seeking to alert consumers about the content of processed foods, thus raising awareness for decision making in order to reduce noncommunicable diseases associated with poor eating habits.

Originality/value

The study provides evidence on the effect of NWs for processed foods on consumer decisions based on the TPB.
Numerical simulation of the area shrinkage mass for the waist of elastic pantyhose by using FEM
Authors: Dan Rui , Shi Zhen
Published: October 2019

Purpose

The area shrinkage of the body under pressure is very important to evaluate the comfort of pressure sense, and it is an important index that appraises compression garment. The purpose of this paper is to obtain the area shrinkage mass of the waist cross section by using the finite-element method (FEM), and the waist of women’s pantyhose could be designed with a different degree of elasticity during the course of design based on clothing pressure comfort.

Design/methodology/approach

This study aimed at the problems existing in the wearing of women’s elastic pantyhose, took the waist of pantyhose as the research object, and the contact between human body and pantyhose as elastic contact. The finite-element model of the waist cross section and elastic pantyhose fabric was acquired through CT scan and Mimics software. After simulating on the corresponding displacement distribution of the waist of sample elastic pantyhose during the process of dressing by using ANSYS, the authors divided the waist cross section into 24 equal regions according to angle (every 15 degrees as a region), and then the area shrinkage mass of each region was obtained by area calculation formula. According to the tendency of area shrinkage distribution, the waist of women’s elastic pantyhose could be designed for different regions of tension considering the pressure comfort, so as to guarantee that the wearing comfort can be maintained on the premise of ensuring the functionality of the elastic pantyhose.

Findings

In this paper, the authors obtained the area shrinkage mass of elastic pantyhose at waist cross section, and this area shrinkage distribution could be used as an objective evaluation index for pressure comfort. All these solutions are of great significance to the optimization design of pantyhose and can provide theoretical basis for the structural improvement of functional pantyhose and the prediction of clothing pressure.

Originality/value

This paper simulated the area shrinkage mass for the waist of elastic pantyhose by using FEM, and the waist of women’s elastic pantyhose could be designed for different regions of tension considering the pressure comfort according to the area shrinkage distribution tendency, so as to guarantee the wearing comfort during the wearing process.
Intergenerational exchange and the possibilities of role substitution for older people
Authors: Macfarlane Joanna , Stephens Christine , Taylor Joanne
Published: October 2019

Purpose

Role loss or substitution are common experiences of older adults, and a role typically held by older people – great grandparent or grandparent – is now under threat. Set within the context of a retirement village where an Intergenerational Programme (IGP) was taking place, the purpose of this paper is to understand older people’s perspectives on preschool-aged children, and the roles they adopt with them.

Design/methodology/approach

The authors conducted semi-structured interviews and analysed the data using narrative analysis (n=19).

Findings

Four narratives were identified, revealing that older adults adopt the roles of teacher and compromiser when interacting with children, believe they are “plugging a gap” in society through their involvement with younger generations and are reminded of life when with them.

Research limitations/implications

The study does not feature the voice of younger children within intergenerational contact; information which would have provided a different perspective on the roles identified.

Social implications

The bulk of global IGP practice is targeted at bringing together older and younger people who are not as young as preschool age, but this may be an opportunity missed. Retirement village operators may also want to consider intergenerational activity with preschool-aged children as a way for them to provide opportunities for role substitution within this environment.

Originality/value

The findings identify a positive perception older people have about young children in today’s society, expanding on very limited literature. How older adults perceive their role with young children is also identified within this research, highlighting how interacting with non-related preschoolers can provide some older people with a substitute role in later years.
Priority effects will impede range shifts of temperate tree species into the boreal forest
Authors: Solarik Kevin A. , Cazelles Kevin , Messier Christian , Bergeron Yves , Gravel Dominique
Published: October 2019

Temperate tree species are expected to expand their distribution into the boreal forest in response to climate change. However, it is becoming increasingly clear that many species will experience significant setbacks in capacity to migrate due to a series of unfavourable conditions impacting their recruitment success, and thus their ability to colonize new locations.

We quantify the relative influence of a series of factors important for tree seedling recruitment at range margins: propagule dispersal, substrate favourability and the influence of the local hetero‐specific species canopy composition. We hypothesized that boreal trees are responsible for priority effects that influence the establishment of temperate tree species seedlings. To do so, we analysed two recruitment stages (first‐year seedlings and older seedlings) for seven tree species: Abies balsamea (ABBA), Acer rubrum (ACRU), Acer saccharum (ACSA), Betula papyrifera (BEPA), Betula alleghaniensis (BEAL), Populus tremuloides (POTR) and Fagus grandifolia (FAGR) commonly found within the temperate‐boreal ecotone forests of northeastern North America.

Overall, we found that boreal canopy trees influence the distribution of substrates, more specifically the occurrence of needle cover and decayed wood in recruitment plots. Interestingly, decayed wood was a poor substrate in almost all cases. This association between canopy and substrate led to highly unfavourable substrates that affected the seedling densities of all temperate tree species. In addition, we found that seedling dispersion was highly localized, where the mean dispersal distance of all trees occurred in close proximity of parent trees.

Synthesis. Unfavourable substrates and limited mean dispersal distance of trees due to resident boreal trees generate (strong) priority effects within the temperate‐boreal ecotone. Together, these conditions promise to cause significant lags in temperate tree species migration into the boreal forest in the future.
Symbiotic interactions above treeline of long‐lived pines: Mycorrhizal advantage of limber pine (Pinus flexilis) over Great Basin bristlecone pine (Pinus longaeva) at the seedling stage
Authors: Shemesh Hagai , Boaz Briana E. , Millar Constance I. , Bruns Thomas D.
Published: October 2019

In response to contemporary changes in climate, many tree species are shifting upslope to find favorable habitat. In the case of obligate ectomycorrhizal species, seedling growth above upper treeline depends on fungal spore availability. In the mountain ranges of the Great Basin, a recent shift in tree species stratification has been recorded, with limber pine (LP, Pinus flexilis) leapfrogging above the ancient bristlecone pine (BCP, Pinus longaeva) forest and establishing above current treeline.

We compared the ability of LP and BCP to interact with soil spore banks collected at different microhabitats (next to dead trees, young live trees or in a treeless control) above current treeline in the White Mountains of California.

We found an ectomycorrhizal fungal spore bank community composed of 15 species that was dominated by an undescribed and a hitherto unsequenced species of Geopora and Rhizopogon, respectively. This represents a much richer community than was found previously in this system. While both LP and BCP were able to establish ectomycorrhiza, LP was twice as likely to do so, and when comparing only seedlings that were colonized, its root system was colonized to a three‐fold greater extent. BCP seedlings grown on soils collected under young live trees were much more likely to be colonized compared to soils from the other two microhabitats.

Synthesis. These differences in ectomycorrhizal receptivity might help to explain why LP is currently establishing at higher rates above the BCP treeline. Furthermore, it is possible that LP saplings above treeline can provide ectomycorrhizal facilitation for BCP seedlings, enabling the subsequent shift of BCP above treeline.
A crosstalk between c‐di‐GMP and cAMP in regulating transcription of GcsA, a diguanylate cyclase involved in swimming motility in Pseudomonas putida
Authors: Xiao Yujie , Liu Huizhong , He Meina , Nie Liang , Nie Hailing , Chen Wenli , Huang Qiaoyun
Published: October 2019

The ubiquitous bacterial second messenger c‐di‐GMP is synthesized by diguanylate cyclase (DGC) and degraded by phosphodiesterase (PDE). Pseudomonas putida has dozens of DGC/PDE‐encoding genes in its genome, but the phenotypical–genotypical correlation and transcriptional regulation of these genes are largely unknown. Herein, we characterize function and transcriptional regulation of a P. putida c‐di‐GMP‐metabolizing enzyme, GcsA. GcsA consists of two per‐ARNT‐sim (PAS) domains, followed by a canonical conserved central sequence pattern (GGDEF) domain and a truncated EAL domain. In vitro analysis confirmed the DGC activity of GcsA. The phenotypic observation revealed that GcsA inhibited swimming motility in an FlgZ‐dependent manner. In terms of transcriptional regulation, gcsA was found to be cooperatively regulated by c‐di‐GMP and cAMP via their effectors, FleQ and Crp respectively. The transcription of gcsA was promoted by c‐di‐GMP and inhibited by cAMP. In vitro binding analysis revealed that FleQ indirectly regulated the transcription of gcsA, while Crp directly regulated the transcription of gcsA by binding to its promoter. Besides, an inverse relationship between the cellular c‐di‐GMP and cAMP levels in P. putida was confirmed. These findings provide basic knowledge regarding the function and transcriptional regulation of GcsA and demonstrate a crosstalk between c‐di‐GMP and cAMP in the regulation of the expression of GcsA in P. putida.
Toytree: A minimalist tree visualization and manipulation library for Python
Authors: Eaton Deren A. R.
Published: October 2019

Toytree is a lightweight Python library for programmatically visualizing and manipulating tree‐based data structures. It implements a minimalist design aesthetic and modern plotting architecture suited for interactive coding in IPython/Jupyter.

Tree drawings are generated in HTML using the toyplot library backend, and display natively in Jupyter notebooks with interactivity features. Tree drawings can be combined with other plotting functions from the toyplot library (e.g. scatterplots, histograms) to create composite figures on a shared coordinate grid, and can be exported to additional formats including PNG, PDF and SVG.

To parse and store tree data, toytree uses a modified fork of the ete3 TreeNode object, which includes functions for manipulating, annotating and comparing trees. Toytree integrates these functions with a plotting layout to allow node values to be extracted from trees in the correct order to style nodes for plotting. In addition, toytree provides functions for parsing additional tree formats, generating random trees, inferring consensus trees and drawing grids or clouds from multiple trees to visualize discordance.

The goal of toytree is to provide a simple Python equivalent to commonly used tree manipulation and plotting libraries in R, and in doing so, to promote further development of phylogenetic and other tree‐based methods in Python. Toytree is released under the GPLv3 license. Source code is available on GitHub and documentation is available at https://toytree.readthedocs.io.
Understanding decisions to use e‐cigarettes or behavioural support to quit tobacco: a qualitative study of current and ex‐smokers and stop smoking service staff
Authors: Hartwell Greg , Egan Matt , Petticrew Mark
Published: October 2019

Aim

To examine factors influencing current and ex‐smokers’ decisions to use e‐cigarettes or behavioural support, including potential impacts of any differences in perspectives between smokers and their local stop smoking services (SSSs).

Design

Semi‐structured qualitative interviews followed by framework analysis, with the ‘capability’, ‘opportunity’, ‘motivation’ and ‘behaviour’ (COM‐B) model of behaviour change used to frame findings.

Setting

SSSs and surrounding local areas in England.

Participants

Interviewees (n = 46) were current or recent smokers (n = 29) and SSS staff or stakeholders (n = 17).

Measurements

Interview topic guides explored influences on smokers' choice of quit method and characteristics of support offered by local SSSs.

Findings

Current and ex‐smokers showed a range of views on potential risks from long‐term vaping, which appeared to be particularly relevant for the capability dimension of COM‐B. These different attitudes to vaping appeared to be linked to variations in people's perceived capability to assess evidence around e‐cigarettes’ safety. Motivations for using or avoiding e‐cigarettes and SSSs often appeared to overlap: attitudes to both e‐cigarettes and nicotine replacement therapy from SSSs often reflected personal experiences and views on whether switching from smoking to these alternatives represented successful quitting or simply ongoing nicotine addiction. For smokers, opportunities to use e‐cigarettes or SSSs appeared to be largely determined by perceived time requirements. Furthermore, interviews with SSS professionals suggested that opportunities to access SSSs for ex‐smokers who were now regular vapers may be being influenced by different e‐cigarette policies adopted in individual areas.

Conclusions

In England, smokers’ decisions to use e‐cigarettes and local stop smoking services appear to be determined by varied influences across the COM‐B framework. Both smokers and stop smoking service professionals display diverse views about potential risks from e‐cigarettes, which has relevance for the provision of behavioural support as well as the uptake of vaping.
Validation of a comorbidity index for use in obstetric patients: A nationwide cohort study
Authors: Bliddal Mette , Möller Sören , Vinter Christina A. , Rubin Katrine H. , Gagne Joshua J. , Pottegård Anton
Published: October 2019

Introduction

A previously developed Obstetric Comorbidity Index has been validated in highly selected cohorts. Validation of the index in an unselected population as well as in other health registers is, however, of high importance to determine external validity.

Material and methods

Using nationwide registers, we formed a nationwide cohort including completed pregnancies (both live‐ and stillborn) in Denmark from 2000 through 2014. Maternal age and 20 comorbid conditions were assessed and weighted. Outcomes were maternal end‐organ injury or death within 30 days postpartum. The index's predictive and discriminative ability was estimated by Brier score and the area under the receiver operating characteristic curve (AUC), respectively. Logistic regression analysis was used to estimate odds ratios (OR) with 95% confidence interval (CI).

Results

In 876 496 completed pregnancies by 527 079 women, 1.40% (n = 12 314) experienced an outcome. The majority of women (64.1%) did not have any record of a condition included in the index and only 0.3% (n = 3044) had a score >6. The incidence of an outcome increased with increasing comorbidity score from 0.9% (95% CI 0.8‐0.9) in women scoring 0% to 10.4% (95% CI 7.6‐13.9) in women scoring 9‐10. Compared with women scoring 0, a score of 1‐2 yielded an OR of 2.34 (95% CI 2.25‐2.44), 3‐4 an OR of 5.16 (95% CI 4.81‐5.54), 5‐6 an OR of 4.84 (95% CI 4.31‐5.44), and 8‐9 an OR of 7.97 (95% CI 6.54‐9.72) for experiencing the outcome. The index had a Brier score of 0.01 and an AUC of 0.64.

Conclusions

Despite potential weaknesses in the outcome definition, the Obstetric Comorbidity Index showed a moderate ability to discriminate and predict end‐organ injury and death in a nationwide cohort in Denmark, in accordance with previous findings. These results suggest that the index may be a useful tool to control for confounding in health research and clinically to identify women at high risk for adverse maternal outcomes.
Target populations to reduce cesarean rates after induced labor: A national population‐based cohort study
Authors: Blanc‐Petitjean Pauline , Schmitz Thomas , Salomé Marina , Goffinet François , Le Ray Camille ,   for the MEDIP Study Group
Published: October 2019

Introduction

Great variations in cesarean rates after induction of labor exist and reasons for these disparities remain unclear. They may be explained by individual characteristics or obstetric practices. Ten‐group classification systems have proved their utility to monitor cesarean rates in general population. We aimed to identify groups of women that account for most cesareans after induction of labor using the Nippita reproducible 10‐group classification, specifically designed for induced population.

Material and methods

A prospective population‐based cohort study was performed in 94 French maternity units, including 3042 women undergoing induction of labor. Women were sorted according to 10 mutually exclusive groups based on parity, weeks of gestation, number of fetuses, fetal presentation and previous cesarean delivery. Relative size, cesarean delivery rate and contribution to the overall cesarean rate were described for each group. Cesarean rates were compared according to the Bishop score at the onset of labor induction. Indications for cesarean delivery were also described in the groups that contributed most to the overall cesarean rate. The MEDIP protocol was registered in ClinicalTrial (NCT02477085).

Results

The overall cesarean rate was 21.0% among this population of induced women. Nulliparous women with a term singleton cephalic fetus (groups 1, 2 and 3; at 37‐38, 39‐40 and ≥41 weeks of gestation, respectively) accounted for two‐thirds of the overall cesarean rate because they were the largest group (relative size of 10.6, 16.6 and 18.1%, respectively) and had higher cesarean rates (27.2, 30.9 and 33.0%, respectively). When the Bishop score was <6 (n = 2270/3042), cesarean delivery rates were higher (24.1 vs 10.7% if Bishop score ≥6, P < 0.01), in particular for group 1 (29.1 vs 12.5%, P = 0.02), and group 2 (33.3 vs 19.3%, P = 0.01). In groups 1, 2 and 3, which contributed most to the overall cesarean rate, a significant part of the cesareans were performed before 6 cm of cervical dilation for dystocia only (40.0, 16.7 and 17.6%, respectively).

Conclusions

Nulliparous women with a term singleton cephalic fetus and an unfavorable cervix represent the population to target for auditing induction practices. Specific actions could be implemented among this population to weigh the benefits and risks of induction and improve the management of labor induction.
Synthetic hydrosilicate nanotubes induce low pro‐inflammatory and cytotoxic responses compared to natural chrysotile in lung cell cultures
Authors: Skuland Tonje , Maslennikova Tatiana , Låg Marit , Gatina El´mira , Serebryakova Maria K. , Trulioff Andrey S. , Kudryavtsev Igor V. , Klebnikova Natalia , Kruchinina Irina , Schwarze Per E. , Refsnes Magne
Published: October 2019

Asbestos (Mg‐hydrosilicate; chrysotile) is known to cause pleural diseases, pulmonary fibrosis and lung cancers, via mechanisms strongly depending on diameter‐length ratio and possibly metal content. A critical question is whether synthetic hydrosilicate nanotubes (NTs) of short length possess little toxic potential compared to chrysotile. Five Mg‐ and two NiNTs of different lengths were assessed for cytotoxicity and pro‐inflammatory responses in THP‐1 macrophages and human bronchial epithelial lung cells (HBEC3‐KT), in comparison with chrysotile. NT lengths/diameters were characterized by TEM, surface areas by BET‐ and BJH analysis, and chemical composition by XRD. The different Mg‐ and NiNTs induced little cytotoxicity in both cell models, in contrast to chrysotile that induced marked cytotoxicity. The two longest synthetic MgNTs, with median lengths of 3 and 5 µm, induced increased levels of pro‐inflammatory cytokines in THP‐1 macrophages, but much less than chrysotile (median length 15 µm) and silica nanoparticles (Si10). The shortest NTs did not induce any increase in cytokines. In HBEC3‐KT cells, all synthetic NTs induced no or only small changes in cytokine responses, in contrast to chrysotile and Si10. The synthetic NTs induced lower TGF‐β responses than chrysotile in both cell models. In conclusion, the pro‐inflammatory responses were associated with the length of synthetic hydrosilicate NTs in THP‐1 macrophages, but not in HBEC3‐KT cells. Notably, the shortest NTs showed no or little pro‐inflammatory activity or cytotoxicity in both cell models. Such a safety by design approach is important for development of new materials being candidates for various new products.
Interaction potential between clarithromycin and individual statins—A systematic review
Authors: Hougaard Christensen Mette Marie , Bruun Haastrup Maija , Øhlenschlæger Thomas , Esbech Peter , Arnspang Pedersen Sidsel , Bach Dunvald Ann‐Cathrine , Bjerregaard Stage Tore , Pilsgaard Henriksen Daniel , Thestrup Pedersen Andreas James
Published: October 2019

The high prevalence of statin and clarithromycin utilization creates potential for overlapping use. The objectives of this MiniReview were to investigate the evidence base for drug‐drug interactions between clarithromycin and currently marketed statins and to present management strategies for these drug combinations. We conducted a systematic literature review following PRISMA guidelines with English language studies retrieved from PubMed and EMBASE (from inception through March 2019). We included 29 articles (16 case reports, 5 observational, 5 clinical pharmacokinetic and 3 in vitro studies). Based on mechanistic/clinical studies involving clarithromycin or the related macrolide erythromycin (both strong inhibitors of CYP3A4 and of hepatic statin uptake transporters OATP1B1 and OATP1B3), clarithromycin is expected to substantially increase systemic exposure to simvastatin and lovastatin (>5‐fold increase in area under the plasma concentration‐time curve (AUC)), moderately increase AUCs of atorvastatin and pitavastatin (2‐ to 4‐fold AUC increase) and slightly increase pravastatin exposure (≈2‐fold AUC increase) while having little effect on fluvastatin or rosuvastatin. The 16 cases of statin‐clarithromycin adverse drug reactions (rhabdomyolysis (n = 14) or less severe clinical myopathy) involved a CYP3A4‐metabolized statin (simvastatin, lovastatin or atorvastatin). In line, a cohort study found concurrent use of clarithromycin and CYP3A4‐metabolized statins to be associated with a doubled risk of hospitalization with rhabdomyolysis or other statin‐related adverse events as compared with azithromycin‐statin co‐administration. If clarithromycin is necessary, we recommend (a) avoiding co‐administration with simvastatin, lovastatin or atorvastatin; (b) withholding or dose‐reducing pitavastatin; (c) continuing pravastatin therapy with caution, limiting pravastatin dose to 40 mg daily; and (d) continuing fluvastatin or rosuvastatin with caution.
Discovery of prolyl hydroxylase 2 inhibitors with new chemical scaffolds as in vivo active erythropoietin inducers through a combined virtual screening strategy
Authors: Yu Zhan , Li Zhihong , Yu Quanwei , Wang Zhi , Song Huilin , Sun Hanyu , Fan Rufeng , Bi Angzhi , Zhang Jun , Zhang Xiaojin
Published: October 2019

Hypoxia‐inducible factor (HIF) is identified to be a promising target to mediate the response to hypoxia. Its stability and activation are negatively controlled by prolyl hydroxylase 2 (PHD2). Thus, PHD2 inhibition has been perceived as a promising anti‐anemia therapy. In this study, we carried out a structure‐based virtual screening followed by in vitro and in vivo biological validation, with the goal to identify novel PHD2 inhibitors. As a result, a set of hits with new chemical scaffolds were revealed to be active in vitro for PHD2 inhibition. Compounds 2 and 3 were revealed to be capable of stabilizing HIF‐α and stimulating erythropoietin (EPO) expression in cell‐based assays. Notably, further in vivo assays revealed that 2 was capable of elevating the EPO plasma levels in C57BL/6 mice model. These findings provide new chemical scaffolds for further development of PHD2 inhibitors.
Clinical diagnostic exome sequencing in dystonia: Genetic testing challenges for complex conditions
Authors: Powis Zöe , Towne Meghan C. , Hagman Kelly D.F. , Blanco Kirsten , Palmaer Erika , Castro Andrew , Sajan Samin A. , Radtke Kelly , Feyma Timothy J. , Juliette Kali , Tang Sha , Sidiropoulos Christos
Published: October 2019

Patients with dystonia are particularly appropriate for diagnostic exome sequencing (DES), due to the complex, diverse features and genetic heterogeneity. Personal and family history data were collected from test requisition forms and medical records from 189 patients with reported dystonia and available family members received for clinical DES. Of them, 20.2% patients had a positive genetic finding associated with dystonia. Detection rates for cases with isolated and combined dystonia were 22.4% and 25.0%, respectively. 71.4% of the cohort had co‐occurring non‐movement‐related findings and a detection rate of 24.4%. Patients with childhood‐onset dystonia trended toward higher detection rates (31.8%) compared to infancy (23.6%), adolescence (12.5%), and early‐adulthood onset (16%). Uncharacterized gene findings were found in 6.7% (8/119) of cases that underwent analysis for genes without an established disease relationship. Patients with intellectual disability/developmental delay, seizures/epilepsy and/or multifocal dystonia were more likely to have positive findings (P = .0093, .0397, .0006). Four (2.1%) patients had findings in two genes, and seven (3.7%) had reclassification after the original report due to new literature, new clinical information or reanalysis request. Pediatric patients were more likely to have positive findings (P = .0180). Our observations show utility of family‐based DES in patients with dystonia and illustrate the complexity of testing.
Non‐enzymatic reaction of carnosine and glyceraldehyde‐3‐phosphate accompanies metabolic changes of the pentose phosphate pathway
Authors: Oppermann Henry , Birkemeyer Claudia , Meixensberger Jürgen , Gaunitz Frank
Published: October 2019

Objectives

Carnosine (β‐alanyl‐l‐histidine) is a naturally occurring dipeptide that selectively inhibits cancer cell growth, possibly by influencing glucose metabolism. As its precise mode of action and its primary targets are unknown, we analysed carnosine's effect on metabolites and pathways in glioblastoma cells.

Materials and methods

Glioblastoma cells, U87, T98G and LN229, were treated with carnosine, and metabolites were analysed by gas chromatography coupled with mass spectrometry. Furthermore, mitochondrial ATP production was determined by extracellular flux analysis and reaction products of carnosine were investigated using mass spectrometry.

Results

Carnosine decreased the intracellular abundance of several metabolites indicating a reduced activity of the pentose phosphate pathway, the malate‐aspartate shuttle and the glycerol phosphate shuttle. Mitochondrial respiration was reduced in U87 and T98G but not in LN229 cells, independent of whether glucose or pyruvate was used as substrate. Finally, we demonstrate non‐enzymatic reaction of carnosine with dihydroxyacetone phosphate and glyceraldehyde‐3‐phosphate. However, glycolytic flux from glucose to l‐lactate appeared not to be affected by the reaction of carnosine with the metabolites.

Conclusions

Carnosine reacts non‐enzymatically with glycolytic intermediates reducing the activity of the pentose phosphate pathway which is required for cell proliferation. Although the activity of the malate‐aspartate and the glycerol phosphate shuttle appear to be affected, reduced mitochondrial ATP production under the influence of the dipeptide is cell‐specific and appears to be independent of the effect on the shuttles.
S3‐Leitlinie: Durchführung des Epikutantests mit Kontaktallergenen und Arzneimitteln – Kurzfassung Teil 1
Authors: Mahler Vera , Nast Alexander , Bauer Andrea , Becker Detlef , Brasch Jochen , Breuer Kristine , Dickel Heinrich , Drexler Hans , Elsner Peter , Geier Johannes , John Swen Malte , Kreft Burkhard , Köllner Arno , Merk Hans , Ott Hagen , Pleschka Silvia , Portisch Maria , Spornraft‐Ragaller Petra , Weisshaar Elke , Werfel Thomas , Worm Margitta , Schnuch Axel , Uter Wolfgang
Published: October 2019

Der diagnostische Standard zum Nachweis einer bestehenden allergischen Kontaktdermatitis ist der Epikutantest. Die vorliegende Leitlinie richtet sich an Assistenz‐ und Fachärzte der Dermatologie, Allergologie und Ärzte weiterer Fachgruppen in Klinik und Praxis, die an der Indikationsstellung oder Durchführung von Epikutantests bei Patienten mit Kontaktekzemen und weiteren Spättypallergien beteiligt sind, sowie Kooperationspartner der Ärzteschaft (Fachberufe im Gesundheitswesen, Kostenträger).

Die Leitlinie zur Durchführung des Epikutantests mit Kontaktallergenen wurde auf der Basis einer systematischen Literatursuche zu definierten Schlüsselfragen evidenzbasiert und im formellen Konsensusverfahren (S3) von Dermatologen unter Einbindung von Pädiatern, Arbeitsmedizinern, Assistenzpersonal und Patientenvertretern erstellt. Bezüglich der methodischen und inhaltlichen Arbeit, auf denen die Empfehlungen basieren, wird auf Methodenbericht und Evidenztabellen verwiesen.

Die Leitlinie stellt allgemeine Aspekte der Epikutantestung sowie medizinrechtlicher Aspekte dar. Es werden Empfehlungen gegeben zur Indikationsstellung, Patientenaufklärung, Auswahl von Testsubstanzen und Kammersystemen, Expositionsort, ‐dauer und Ablesezeitpunkten, Interpretation von Testreaktionen, endogenen und exogenen Einflussfaktoren, Testung besonderer Personengruppen (Kinder, Schwangere, Immunsupprimierte) sowie Risiken und unerwünschten Nebenwirkungen bei der Durchführung des Epikutantests mit Kontaktallergenen.
Increased genetic marker density reveals high levels of admixture between red deer and introduced Japanese sika in Kintyre, Scotland
Authors: McFarlane S. Eryn , Hunter Darren C. , Senn Helen V. , Smith Stephanie L. , Holland Rebecca , Huisman Jisca , Pemberton Josephine M.
Published: October 2019

Hybridization is a natural process at species range boundaries, but increasing numbers of species are hybridizing due to direct or indirect human activities. In such cases of anthropogenic hybridization, subsequent introgression can threaten the survival of native species. To date, many such systems have been studied with too few genetic markers to assess the level of threat resulting from advanced backcrossing. Here, we use 44,999 single nucleotide polymorphisms (SNPs) and the ADMIXTURE program to study two areas of Scotland where a panel of 22 diagnostic microsatellites previously identified introgression between native red deer (Cervus elaphus) and introduced Japanese sika (Cervus nippon). In Kintyre, we reclassify 26% of deer from the pure species categories to the hybrid category whereas in the NW Highlands we only reclassify 2%. As expected, the reclassified individuals are mostly advanced backcrosses. We also investigate the ability of marker panels selected on different posterior allele frequency criteria to find hybrids assigned by the full marker set and show that in our data, ancestry informative markers (i.e. those that are highly differentiated between the species, but not fixed) are better than diagnostic markers (those markers that are fixed between the species) because they are more evenly distributed in the genome. Diagnostic loci are concentrated on the X chromosome to the detriment of autosomal coverage.
Capital and Value in Late Adulthood
Authors: Griffore Robert J.
Published: October 2019

In the present neoliberal context, life is structured within management of capital. Late adulthood is a period of final decision making about human capital and financial capital. In past generations, older adults were supported by social capital systems of family and voluntary care, largely detached from large systems powered by financial capital. Now, late adulthood is about efficient movement of older adults from the workplace to retirement, from families to residential care, and on to death. Late adulthood is structured by efficient management of financial capital for and by systems that produce, manage, and/or deliver medical care, pharmaceuticals, residential care, insurance, investments, banking, death, and other services. In the present analysis, the focus is on financial capital, human capital, and social capital in late adulthood. The paper organizes some concepts and aspects of capital, value, aging, and late adulthood that are common knowledge and experience, for examination and analysis within systemic contexts.
The exigencies of student participation in university governance: Lip services and bottlenecks
Authors: Tamrat Wondwosen
Published: October 2019

This study was conducted to explore the level, type and quality of student participation in the governance milieu of twenty public universities in Ethiopia based on secondary data availed at a national level. The findings reveal that despite their demands and aspirations, students' participation in university governance is still at its lowest ebb across most of Ethiopian public universities both in terms of their representation at the available hierarchical structures and the quality of participation in matters of substantial importance to the student body. Given the multitude of advantages the institutions and students can garner from meaningful student participation, it is argued that changes need to be made in terms of improved representation, type and quality of student participation.
Network analysis of intra‐hospital transfers and hospital onset clostridium difficile infection
Authors: McHaney‐Lindstrom Megan , Hebert Courtney , Miller Harvey , Moffatt‐Bruce Susan , Root Elisabeth
Published: October 2019

Objectives

To explore how social network analysis (SNA) can be used to analyse intra‐hospital patient networks of individuals with a hospital acquired infection (HAI) for further analysis in a geographical information systems (GIS) environment.

Methods

A case and control study design was used to select 2008 patients. We retrieved locational data for the patients, which was then translated into a network with the SNA software and then GIS software. Overall metrics were calculated for the SNA based on three datasets and further analysed with a GIS.

Results

The SNA analysis compared cases to control indicating significant differences in the overall structure of the networks. A GIS visual representation of these metrics was developed, showing spatial variation across the example hospital floor.

Discussion

This study confirmed the importance that intra‐hospital patient networks play in the transmission of HAIs, highlighting opportunities for interventions utilising these data. Due to spatial variation differences, further research is necessary to confirm this is not a localised phenomenon, but instead a common situation occurring within many hospitals.

Conclusion

Utilising SNA and GIS analysis in conjunction with one another provided a data‐rich environment in which the risk inherent in intra‐hospital transfer networks was quantified, visualised and interpreted for potential interventions.
Asian management of hypertension: Current status, home blood pressure, and specific concerns in Korea
Authors: Park Sungha , Shin Jinho
Published: October 2019

Hypertension is present in almost one‐quarter of women and one‐third of men in Korea. Although mortality rates from stroke and myocardial infarction (MI) appear to be decreasing, stroke is a more common cause of cardiovascular death than MI. This may be due to better control of hypertension, but national control rates have remained stable for more than a decade (at about 45%). Korean Society of Hypertension guidelines have recommended the use of home blood pressure monitoring (HBPM) since 2007, but a recent survey suggests that physicians have concerns about the accuracy of HBPM devices. Nevertheless, use of HBPM is indispensable to monitoring and achieving blood pressure (BP) control. Current diagnostic and treatment thresholds and recommendations are based on Asian consensus document guidance. Use of dual combination antihypertensive therapy is slightly more common than use of monotherapy in Korea, while triple combination therapy is used less often. Angiotensin receptor blockers and calcium channel blockers are the most popular choices for antihypertensive therapy and are the most widely used combination. HBPM plays an important role in evaluating and monitoring BP, particularly in Asians. Individualized cardiovascular risk assessment and better BP control are required to prevent cardiovascular diseases, but there is a need for local evidence relating to optimal BP thresholds and targets.
Clinical and tomographic comparison of dental implants placed by guided virtual surgery versus conventional technique: A split‐mouth randomized clinical trial
Authors: Magrin Gabriel L. , Rafael Stela N. F. , Passoni Bernardo B. , Magini Ricardo S. , Benfatti Cesar A. M. , Gruber Reinhard , Peruzzo Daiane C.
Published: October 2019

Aim

Our objective was to compare guided virtual surgery to conventional surgery in terms of angular deviation of single dental implants placed in the posterior mandible.

Materials and Methods

Patients with bilateral homologous single teeth missing in the posterior mandible were eligible for this split‐mouth randomized clinical trial. Cone beam computed tomography (CBCT) was performed for virtual planning of implant position and manufacturing of the stereolithographic guides. One week after the surgery, a second CBCT scan was superimposed to the initial planning. Primary endpoint was the angular deviation between virtual and clinical implant position. Secondary endpoints were linear deviations and patient‐reported outcomes collected with a questionnaire.

Results

Data from 12 patients were available for analysis. Angular deviation was significantly lower using stereolithographic guides as compared to conventional guides (2.2 ± 1.1° vs. 3.5 ± 1.6°, p = .042). Linear deviations were similar for both techniques in the coronal (2.34 ± 1.01 vs. 1.93 ± 0.95 mm) and apical (2.53 ± 1.11 vs. 2.19 ± 1.00 mm) dimensions (p ˃ .05). The selection of the surgical technique had no significant impact on the patient‐reported outcomes.

Conclusion

Our data suggest that the angular discrepancy between the virtual and the clinical implant position is slightly lower when using stereolithographic guides as compared to conventional guides.
A molecular assessment of species diversity in Tympanopleura and Ageneiosus catfishes (Auchenipteridae: Siluriformes)
Authors: Hashimoto Shizuka , Py‐Daniel Lúcia H. Rapp , Batista Jacqueline S.
Published: October 2019

In order to test the congruence of genetic data to the morphologically defined Neotropical catfish genera Tympanopleura and Ageneiosus and explore species diversity, we generated 17 DNA barcodes from five of six species of Tympanopleura and 12 of 13 species of Ageneiosus. To discriminate limits between species, an automatic barcode gap discovery (ABGD), a generalised mixed yule‐coalescent model (GYMC) and fixed distance thresholds Kimura two‐parameter (K2P; 3%) were used to discriminate putative species limits from the DNA barcodes. The ABGD, GMYC and K2P methods agreed by each generating 13 clusters: six in Tympanopleura (five nominal plus one undescribed species) and seven in Ageneiosus. These clusters corresponded broadly to the described species, except in the case of the Ageneiosus ucayalensis group (A. akamai, A. dentatus, A. intrusus, A. ucayalensis, A. uranophthalmus and A. vittatus). Haplotype sharing and low divergences may have prevented molecular methods from distinguishing these species. We hypothesise that this is the result of a recent radiation of a sympatric species group distributed throughout the Amazon Basin. One putative new species of Tympanopleura was also supported by the molecular data. These results taken together highlight the utility of molecular methods such as DNA barcoding in understanding patterns of diversification across large geographic areas and in recognising overlooked diversity.