bluuebunny/crossref_metadata_2025 huggingface dataset:
Grip strength mediates the relationship between muscle mass and frailty
Authors: Choe Yu‐Ri , Jeong Ju‐Ri , Kim Yeon‐Pyo
Published: December 2019

Background

Although sarcopenia and frailty are important diseases in geriatrics, few studies have investigated the association between the two diseases. Thus, this study aimed to examine the relationship between two components of sarcopenia (muscle mass and muscle function) and frailty.

Methods

In total, 997 Korean older adults (456 men and 541 women) were included in this cross‐sectional observational study. We used a polynomial linear regression analysis to obtain standardized sex, age, and height‐adjusted appendicular skeletal muscle mass (zASM), as well as to standardized sex, age, and height‐adjusted grip strength (zGS). We then performed a causal mediation analysis to confirm the relationship between zASM and frailty.

Results

In both men and women, zGS mediated the relationship between zASM and frailty (average causal mediation effect in men: −0.096 {−0.159 to −0.050}; in women: −0.053 {−0.098 to −0.010}). For every one‐point increase in zGS score, the relative risk of a one‐point increase in frailty was reduced by 21% in men (e−0.238 = 0.788) and by 11% in women (e−0.113 = 0.893).

Conclusions

In this study on Korean older adults, muscle mass did not have a direct effect on frailty but had an indirect effect through altered muscle function.
Relapse of anxiety‐related fear and avoidance: Conceptual analysis of treatment with acceptance and commitment therapy
Authors: Smith Brooke M. , Smith Gregory S. , Dymond Simon
Published: December 2019

Excessive fear and avoidance in relatively safe situations can lead to a narrowing of one's behavioral repertoire and less engagement with valued aspects of living. Ultimately, these processes can reach clinical levels, as seen in anxiety, trauma, and obsessive–compulsive disorders. Research on the basic behavioral processes underlying successful treatment with exposure therapy is growing, yet little is known about the mechanisms contributing to clinical relapse. Until recently, these mechanisms have largely been conceptualized in terms of Pavlovian return of fear, with relatively little research into operant processes. In the current paper, we briefly review translational research in anxiety disorders and the connections between fear and avoidance, focusing on recent work in the acquisition, extinction, and relapse of avoidance behavior and the generalization of this learning through arbitrary symbolic relations. We then introduce one possible treatment approach to mitigating clinical relapse, acceptance and commitment therapy (ACT), and provide a conceptual analysis for why ACT may be especially well‐situated to address this issue. Finally, we end with potential directions for future research on treatment and relapse of anxiety disorders.
Microwave‐assisted rapid and efficient synthesis of chromene‐fused pyrrole derivatives through multicomponent reaction and evaluation of antibacterial activity with molecular docking investigation
Authors: Baral Nilofar , Mishra Deepak Ranjan , Mishra Nilima Priyadarsini , Mohapatra Seetaram , Raiguru Bishnu Prasad , Panda Pravati , Nayak Sabita , Nayak Mukesh , Kumar P. Sudhir
Published: December 2019

The current study aimed to identify a new strategy of FeCl3 catalyzed multicomponent synthesis of substituted 2H‐chromene–fused pyrrole derivatives. A series of chromene‐based pyrrole prepared by employing an array of 3‐nitro‐2H‐chromenes, aniline, and acetylacetone in toluene under microwave irradiation. Using FeCl3 as a prompt catalyst and microwave irradiation to synthesize 2H‐chromene–fused pyrrole motifs significantly reduces the reaction time and facilitates to high yields (83%‐95%). Structure of all synthesized compounds analyzed by spectroscopic analysis. One‐pot reaction, short reaction period, and simple experimental procedure are the fascinating properties associated with this protocol. The in vitro antibacterial activity of the entire series was assessed against Staphylococcus aureus and Escherichia coli. Out of all the compounds, 15b and 15h revealed most excellent potency against both the bacterial strains relative to the reference gentamicin. Docking study was employed to determine the possible binding orientation of DNA gyrase with the active sites of chromene‐fused pyrrole analog. The docking results show that compounds 15b and 15h have higher binding affinity with energy −8.00 and −8.80 kcal/mol. These results illuminate the mode of binding progression and provide an esteemed pathway for the design and the structural modification of chromene‐fused pyrroles as a newly advanced class of antibacterial agent.
CsF promoted rapid synthesis of spirooxindole‐pyran annulated heterocycles at room temperature in ethanol
Authors: Wagh Yogesh B. , Padvi Swapnil A. , Mahulikar Pramod P. , Dalal Dipak S.
Published: December 2019

A newer, versatile, and straightforward synthetic strategy for the construction of functionalized spirooxindole‐pyran annulated heterocycles is described. The procedure is based on CsF‐promoted rapid tandem Knoevenagel‐Michael‐Cyclocondensation reaction of isatin, malononitrile, and 4‐hydroxycoumarin/barbituric acids/pyrazolone at room temperature in ethanol. This methodology has various advantages like easy operational, excellent yields within short reaction time (3‐25 min), and simple isolation of products. The CsF has a dual role as a base and carbonyl activator.
THE POTENTIAL OF PROBLEM‐BASED LEARNING TO ENHANCE ENGINEERING EDUCATION IN AFRICAN UNIVERSITIES
Authors: Abbott D. , Chipika S. , Wilson G.
Published: December 2019

Engineering education underpins local capacity. As such, it forms a key component of sustainable engineering for development. While education is needed at all levels, this paper focuses on the tertiary level where it is assumed that graduating students aspire to become professional engineers. In much of Africa, however, university engineering education is criticised for being little changed since the early independence period. It uses outdated pedagogy, lacks professional relevance and fails to attract a diverse range of students. Through contrasting case studies, the paper examines, therefore: (i) the potential to move curriculum towards a problem‐based learning pedagogy where students focus on real‐world problems and associated engineering solutions; and (ii) the contribution of diverse case studies to this pedagogy and the content of courses. We argue that these twin shifts will broaden the curriculum beyond its habitual industry and physical infrastructure focus, is attractive to a wider range of students and links to human development as expressed through the United Nations sustainable development goals. It is also a major component in the pursuit by African institutions for international recognition of the quality of their engineering programmes. © 2019 John Wiley & Sons, Ltd.
Ownership and Participation in Local–Global Partnerships: The Recovery of Shelter and Settlements after Humanitarian Crises
Authors: Babister Elizabeth
Published: December 2019

Local actors affected by humanitarian crises, including disasters and conflict, often attract the support of global actors with engineering resources to support the recovery of their shelter and settlements. Global initiatives increasingly prioritise the agency of local actors and the concept of local participation following humanitarian crises, and a critical mass of evidence of the role of local actors in the recovery of their shelter and settlements has now emerged. This study reviews this body of knowledge and considers its implications on the global humanitarian policy framework. Data have been collected from emerging literature on the recovery of shelter and settlements and extended with sampling cases of 25 crises over the past two decades. This study finds that for the successful recovery of shelter and settlements, the participation of affected households must prioritise their ownership of the recovery process, rather than simply their level of involvement. Furthermore, a focus on local participation appears to be most successful when tailored to the capacity households have to contribute and the shape of their plans for recovery. At the level of global humanitarian policy, a shift in priorities is required if local ownership and successful recovery is to be achieved. These priorities include more broadly assessing local capacity during the immediate aftermath of crisis, paired with systematically funding beyond the first 12 months after a crisis with adaptive funding instruments. The focus of this paper is the recovery of shelter and settlements, but the analysis could be used more generally in other contexts where the need for rapid global response with financial, technical and engineering knowledge coincides with the need to work with local social, political and technical knowledge and experiences.
Morphology and evolution of the snake cornea
Authors: Da Silva Mari‐Ann Otkjær , Gade Jacob Thorup , Damsgaard Christian , Wang Tobias , Heegaard Steffen , Bertelsen Mads Frost
Published: December 2019

To investigate whether the thickness of the cornea in snakes correlates with overall anatomy, habitat or daily activity pattern, we measured corneal thickness using optical coherence tomography scanning in 44 species from 14 families (214 specimens) in the collection at the Natural History Museum (Denmark). Specifically, we analyzed whether the thickness of the cornea varies among species in absolute terms and relative to morphometrics, such as body length, spectacle diameter, and spectacle thickness. Furthermore, we examined whether corneal thickness reflects adaptation to different habitats and/or daily activity patterns. The snakes were defined as arboreal (n = 8), terrestrial (n = 22), fossorial (n = 7), and aquatic (n = 7); 14 species were classified as diurnal and 30 as nocturnal. We reveal that the interspecific variation in corneal thickness is largely explained by differences in body size, but find a tendency towards thicker corneas in diurnal (313 ± 227 μm) compared to nocturnal species (205 ± 169 μm). Furthermore, arboreal snakes had the thickest corneas and fossorial snakes the thinnest. Our study shows that body length, habitat, and daily activity pattern could explain the interspecific variation in corneal morphology among snakes. This study provides a quantitative analysis of the evolution of the corneal morphology in snakes, and it presents baseline values of corneal thickness of multiple snake species. We speculate that the cornea likely plays a role in snake vision, despite the fact that results from previous studies suggest that the cornea in snakes is not relevant for vision (Sivak, Vision Research, 1977, 17, 293–298).
Laboratory Raman and VNIR spectroscopic studies of jarosite and other secondary mineral mixtures relevant to Mars
Authors: Liu Changqing , Ling Zongcheng , Zhang Jiang , Bi Xiangyu , Xin Yanqing
Published: December 2019

Jarosite is an indicator of ephemeral, acidic fluids in Martian history, which often occurs with some other secondary minerals based on Mars in situ and remote sensing detections. However, detailed Raman and visible and near‐infrared (VNIR) spectroscopic studies of jarosite and other secondary mineral mixtures relevant to Mars still lack, which are essential for jarosite identifications and hence a better understanding of Martian aqueous history. In this study, we prepared 44 binary mixtures of jarosite with four other secondary minerals (alunite, gypsum, kaolinite, and montmorillonite), and characterized their detailed Raman and VNIR spectral features. We find the Raman spectral patterns of jarosite, alunite and gypsum are distinctive and ready for their identification in mixtures, although mixtures with montmorillonite and kaolinite show high fluorescence background and their Raman spectral features are obscured by strong and sharp peaks of jarosite. The normalizing strengths of their characteristic Raman spectral features (e.g., ν1 for jarosite) change with jarosite mass fractions, and mineral distribution maps and volume percentages of endmembers are acquired using Raman imaging method. The band depths of absorption features in VNIR spectra are also correlated with jarosite mass proportions, and four models are proposed to evaluate jarosite mass fractions in the mixtures using a partial least squares algorithm. These detailed spectral properties of mixtures and models would provide valuable information for in situ Raman investigations on Mars (e.g., ExoMars and Mars 2020) and orbital VNIR remote sensing detections (e.g., Compact Reconnaissance Imaging Spectrometer for Mars).
A pilot study on high wavenumber Raman analysis of human dental tissues
Authors: He Wencai , Livingston Jordan C. , Sobiesk Evan R. , Zhou Jiange , Zhu Xianchun , Duan Yuanyuan , Yang Shan
Published: December 2019

Water plays a critical role in dental tissues including enamel and dentin. The characterization of water structure was primarily conducted by nuclear magnetic resonance. Raman spectroscopy is a powerful analytic technology with capability for structure analysis in materials. However, acquiring high wavenumber Raman signals from dental tissues was challenging due to either the fluorescence interference under laser illumination or reduced sensitivity of charge‐coupled device based detectors. In this study, we demonstrate a pilot research on high wavenumber Raman analysis in dental tissues using a customized Raman spectrometer based on an InGaAs detector. A signal located at 3,570 cm−1 is found dominating the O─H region Raman spectra of enamel but is barely detectable from dentin. The profiles of the high wavenumber region Raman spectra change with the locations in enamel, as well as the polarization of the excitation laser beam. The results suggest that the size or crystallinity differences of hydroxyapatite crystals are the main cause of the spectral variation from dentin to enamel and could be partially responsible for the variation among different locations in enamel.
Dissipation of fluazinam in citrus groves and a risk assessment for its dietary intake
Authors: Zhao Junlong , Tan Zhenchao , Wen Yan , Fan Shuai , Liu Chenglan
Published: December 2019

BACKGROUND

Citrus is one of the most important fruit crops worldwide. Fluazinam is a fungicide that is used to control fungal diseases, and its dissipation and residue in citrus fruits should be studied.

RESULTS

A Quick, Easy, Cheap, Effective, Rugged and Safe (QuEChERS) procedure combined with gas chromatography with an electron capture detector (GC‐ECD) has been developed. The fortified recoveries ranged from 82.1% to 105.9%, with relative standard deviations (RSDs) of less than 5.7%. Fluazinam dissipated relatively quickly following first‐order kinetics, with a half‐life of 8.5–9.5 days. The experiments on the terminal residue of fluazinam in citrus were conducted at six locations in China, and the risk quotient (RQ) method was applied to citrus fruits for dietary exposure risk assessment based on the terminal residue test. The RQs of fluazinam at three preharvest intervals (PHIs) (21, 28, and 35 days) were all less than 100%, which is an acceptable level for human consumption. The present study provides a reference for the establishment of maximum residue limit (MRL) for fluazinam in citrus.

CONCLUSIONS

The dissipation and residues of fluazinam in citrus were monitored. The half‐life of less than 10 days showed that fluazinam could degrade relatively easily in citrus. The risk assessment also indicated the intake safety of fluazinam in citrus. © 2019 Society of Chemical Industry
Effect of garden cress in reducing blood glucose, improving blood lipids, and reducing oxidative stress in a mouse model of diabetes induced by a high‐fat diet and streptozotocin
Authors: Chen Xi , Yuan Huaibo , Shi Fangfang , Zhu Yudong
Published: December 2019

BACKGROUND

A mouse model in which diabetes mellitus was induced by low‐dose streptozotocin (STZ) injection combined with a high‐fat diet was used to study the effect of two water cress (Lepidium savitum) preparations. Diabetic mice were treated with dried cress powder or with water‐soluble extracts (tested at two doses), together with proper control groups. The mice were evaluated after 4 weeks of continuous intervention for type 2 diabetic and associated markers. We determined blood glucose, body weight, total cholesterol (TC), triglyceride (TG), low‐density lipoprotein (LDL), high‐density lipoprotein (HDL), serum insulin levels, and DNA integrity of hepatic cells. The concentrations of malondialdehyde (MDA) and lipid peroxide (LPO) and the activities of four enzymes that are part of the antioxidant defense system were determined in liver samples, as well as gene expression (by semi‐quantitative reverse transcription polymerase chain reaction) and enzyme activity of IRS‐1, IRS‐2, PI3K, AKT‐2, and GLUT4.

RESULTS

After 4 weeks of intervention, the levels of TC, TG, and LDL cholesterol were significantly (P < 0.5) decreased and HDL cholesterol was significantly increased. Enzyme activities of liver superoxide dismutase, glutathione, glutathione peroxidase, and catalase were significantly increased, whereas MDA and LPO concentrations were significantly reduced. The transcription level of the five genes assessed was increased, with corresponding increases in protein expression.

CONCLUSION

Oral uptake of garden cress can significantly reduce the blood glucose and improve the blood lipid metabolism of diabetic mice. Considerable improvements in the activity of antioxidant defense enzymes were observed in type 2 diabetic mice that improved the body's antioxidant emergency response. © 2019 Society of Chemical Industry
Development and comparative study of a pat/bar real‐time PCR assay for integrating the screening strategy of a GMO testing laboratory
Authors: Verginelli Daniela , Paternò Annalisa , De Marchis Maria Laura , Quarchioni Cinzia , Vinciguerra Daniela , Bonini Pamela , Peddis Stefania , Fusco Cristiana , Misto Marisa , Marfoglia Cristina , Pomilio Francesco , Marchesi Ugo
Published: December 2019

BACKGROUND

The number and variety of genetically modified organisms (GMOs) used globally for the production of food and feed, and potentially circulating in the European Union (EU), is constantly increasing. This implies an additional effort for the EU enforcement laboratories to optimize available resources, to contain costs and time. A well established approach for streamlining the analytical workflow is the introduction of a screening step, typically based on a smart set of real‐time polymerase chain reaction (PCR) screening methods. The multiplexing strategy, allowing the detection of several screening elements simultaneously, is a further optimization of this step.

RESULTS

In this study, we present the validation of a real‐time PCR duplex assay for the pat and bar screening elements to be easily incorporated in the GMO diagnostic routine. We also provide a comparison between this method and the related singleplex and pre‐spotted assays.

CONCLUSION

Our results fully respect all the validation parameters suggested by the Minimum Performance Criteria of the European Network of GMO Laboratories. Furthermore, the duplex assay is equivalent in terms of performance compared to the other two methods, but it shows a higher overall flexibility and cost effectiveness. © 2019 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
Characterization and identification of the metabolites of Menthae Haplocalycis Herba water extracts in rat plasma, urine, and feces by ultra‐high performance liquid chromatography with linear ion trap‐Orbitrap mass spectrometry
Authors: Zhang Wei , Xu Lu‐lu , Yu Xiao , Jiang Yan‐yan , Zhang Jia‐yu , Liu Bin
Published: December 2019

Menthae Haplocalycis Herba has been utilized for food and medicinal purposes in China for thousands of years. It has various efficacies, including dispelling wind and heat and relieving sore throat. M. Haplocalycis Herba has been also widely used in food, cosmetics, spices, and other fields. Exploring the constituents and detecting the metabolites of M. Haplocalycis are of great significance to clarify the effective substances. However, the in vivo metabolites of M. Haplocalycis Herba water extract are still unclear. Herein, a sensitive and specific method, ultra‐high performance liquid chromatography with linear ion trap‐Orbitrap mass spectrometry, established in this assay was used to study the metabolism of M. Haplocalycis Herba water extract in rat plasma, urine, and feces. We characterized and identified 9, 50, and 34 metabolites in plasma, urine, and feces, respectively. Seven metabolic pathways, including phase Ⅰ (isomerization, demethylation, hydroxylation, and dehydration) and phase Ⅱ (sulfation and glucuronidation) were mainly involved in the metabolism. It is the first systematic study on the metabolism of M. Haplocalycis Herba water extract in vivo, which enrich current understanding of the metabolic behavior of M. Haplocalycis Herba water extract and provide a metabolic rationale for further in‐depth in vivo biotransformation and pharmacokinetic analysis.
When truth is power: Institutional ethnography of a think tank
Authors: Xiao Honggen , Dai Bin
Published: December 2019

This study offers an institutional ethnography of a tourism think tank in a large origin/destination economy. The roles of China Tourism Academy as advisors, academics, advocates, and brokers are discussed in the context of theory and practice, where government think tank researchers are found to be speaking truth both to and for power as they develop an ambition or sense of loftiness of serving and contributing to the state through doing research and mobilizing knowledge (zhishi baoguo). Although the inquirers' positions or perspectives should be acknowledged, this ethnography contributes to future research into think tanks or other knowledge agencies in different origin/destination societies.
Cobalt‐promoted MoS2 nanosheets: A promising novel diesel hydrodesulfurization catalyst
Authors: Abbasi Ali , Karimi Ali , Aghabozorg Hamidreza , Sadighi Sepehr , Aval Maryam Alizadeh
Published: December 2019

MoS2 has been commonly used as a catalyst in hydrodesulfurization (HDS) of petroleum cuts in crude oil refineries. In this study, the synthesis of unsupported MoS2 and Co‐promoted MoS2 nanosheets produced from molybdenum oxide and thiourea is reported. The synthesized samples were characterized by using x‐ray fluorescence, x‐ray diffraction, Brunauer–Emmett–Teller (BET), temperature‐programmed reduction, thermal gravimetric analysis, and transmission electron microscopy methods, and then they were utilized for HDS of diesel through a fixed‐bed catalytic reactor. Results indicated that a cobalt promoter affected both the number and the performance of active sites of the molybdenum sulfides, and the activity of the promoted MoS2 catalyst was consistently higher than that of the MoS2 catalyst. More significantly, the activity of the promoted catalyst was slightly declined during 48 h continuous HDS reaction, which indicated the stability of this catalyst. Additionally, during 12 h of test run, the HDS activity of the promoted catalyst was about 60% higher than MoS2 one.
Retracted: Luminescent In(III)‐based coordination polymer for selectively sensing Cr2O72−, antibacterial and anti‐inflammatory effect on the infectious abortion
Authors: Xu Lin‐Fen , Huang Ling‐Na , Lu Yan‐Fang , Chen Xiu‐Juan
Published: December 2019

A novel water‐stable metal‐organic framework based on In(III), namely, [In3(btta)2(OH)3(H2O)]·(DMA)2 (1, DMA = N,N‐dimethylacetamide), constructed from a novel ligand (2E,2′E,2″E)‐3,3′,3″‐(benzene‐1,3,5‐triyl)triacrylic acid (H3btta), was obtained by a solvothermal reaction and structurally characterized by X‐ray diffraction of single crystal along with elemental analysis. Owing to its high porosity and insensitive luminescent emission at room temperature, it was studied as a light‐emitting sensor for detecting toxic Cr2O72− anion in water, which shows high selectivity and sensitivity. To solve the bacterial problem, the protective effect of the compound against bacterial infection after missed abortion was evaluated. In the in vivo model, after the treatment with the compound, the clonal formation unit (CFU) in the uterine tissue was evaluated, and the animal weight was measured and recorded. In addition to this, the level of IL‐18, C‐reactive protein, TNF‐α, as well as IL‐1β within the infectious tissues was detected by the ELISA method. Pose scoring software and molecular docking showed that the compound might bind to the NF‐κB protein, and this might offer a latent regulatory mechanism for the compound.
Does 3D volumetric analysis predict the reach of endoscopically harvested buccal fat pad flap
Authors: Subramaniam Somasundaram , Gomez Matias , Maza Guillermo , Prevedello Daniel M. , Carrau Ricardo L.
Published: December 2019

Objectives

To determine if the volume of buccal fat, ascertained by computed tomography (CT) scanning, would correspond to surface area and reach (length and width) of the flap intraoperatively to aid in the reconstruction of selected skull base defects.

Methods

Cadaveric study of five specimens, 10 sides. Methods CT imaging and evaluation using the Osirix 9 software (Pixmeo; Bernex, Switzerland). of cadaveric heads to calculate the volume of the buccal fat bilaterally. The flap was then harvested endoscopically. Measurements were taken. Two heads were also dissected via a transfacial approach.

Results

The volume of the buccal fat pad (BFP) as well as the maximum length and width of the endoscopically harvested flap were documented. There was a positive correlation shown between the calculated volume of the BFP based on CT imaging and the dissected length and width of the flap (Pearson correlation, r = 0.83 and r = 0.80, respectively). The transfacial dissection demonstrated the lobes of the BFP well, showing that most of the endoscopic mobilization of the BFP was limited to the posterior lobe, in particular to the temporalis and pterygoid components, with minimal displacement of the superficial components. This minimized the risk of visibly hollowing the buccal fullness.

Conclusion

Preoperative calculation of the CT‐based volume of the BFP correlates positively with the intraoperative maximum reach of the flap for both length and width. Whereas the volume may be lower in some instances, the BFP would still have adequate reach to provide coverage for the lower and mid‐clival region in most patients.

Level of Evidence

NA.

Laryngoscope, 130:1670–1673, 2020
Drivers of tropical forest cover increase: A systematic review
Authors: Borda‐Niño Mónica , Meli Paula , Brancalion Pedro H. S.
Published: December 2019

Promoting natural regeneration can be a viable strategy to achieve ambitious restoration commitments, but predicting where native forest cover is likely to expand is challenging. Different biophysical and socioeconomic factors may determine the chances of native forest regrowth at different spatial and temporal scales, producing complex spatial patterns in the landscape and adding more and deeper information about potential for different forms of forest restoration. On the basis of a systematic literature review including 64 peer‐reviewed articles from the global tropics and subtropics published from 1990 to 2017, we assessed the methodologies employed to remotely detect forest cover increase and to identify its biophysical and socioeconomic drivers. Automatic classification of multitemporal images and transition matrices were the most popular methods to detect areas of forest regrowth, whereas regression analysis was the most used analytical approaches to assess drivers. Forest cover increased more often on steeper slopes, close to forest remnants, inside protected areas, and far from population centers. However, the effects of most drivers varied among scales of evaluation and may be further affected by the scale of forest regrowth. The most influential biophysical and socioeconomic drivers of forest cover increase identified here can be used to develop predictive models on the likelihood of native forest regrowth to guide the implementation of cost‐effective tropical forest restoration, thus contributing to the mitigation of climate change and species extinction. Current remote‐sensing literature evaluating forest cover changes seems to be largely focused on deforestation dynamics, with little attention given to forest cover increase.
The European medical information framework: A novel ecosystem for sharing healthcare data across Europe
Authors: Lovestone Simon ,   EMIF Consortium
Published: December 2019

Introduction

The European medical information framework (EMIF) was an Innovative Medicines Initiative project jointly supported by the European Union and the European Federation of Pharmaceutical Industries and Associations, that generated a common technology and governance framework to identify, assess and (re)use healthcare data, to facilitate real‐world data research. The objectives of EMIF included providing a unified platform to support a wide range of studies within two verification programmes—Alzheimer's disease (EMIF‐AD), and metabolic consequences of obesity (EMIF‐MET).

Methods

The EMIF platform was built around two main data‐types: electronic health record data and research cohort data, and the platform architecture composed of a set of tools designed to enable data discovery and characterisation. This included the EMIF catalogue, which allowed users to find relevant data sources, including the data‐types collected. Data harmonisation via a common data model were central to the project especially for population data sources. EMIF also developed an ethical code of practice to ensure data protection, patient confidentiality and compliance with the European Data Protection Directive, and GDPR.

Results

Currently 18 population‐based disease agnostic and 60 cohort‐based Alzheimer's data partners from across 14 countries are contained within the catalogue, and this will continue to expand. The work conducted in EMIF‐AD and EMIF‐MET includes standardizing cohorts, summarising baseline characteristics of patients, developing diagnostic algorithms, epidemiological studies, identifying and validating novel biomarkers and selecting potential patient samples for pharmacological intervention.

Conclusions

EMIF was designed to provide a sustainable model as demonstrated by the sustainability plans for EMIF‐AD. Although network‐wide studies using EMIF were not conducted during this project to evaluate its sustainability, learning from EMIF will be used in the follow‐on IMI‐2 project, European Health Data and Evidence Network (EHDEN). Furthermore, EMIF has facilitated collaborations between partners and continues to promote a wider adoption of principles, technology and architecture through some of its continued work.
Restructuring a correlated multilevel decision hierarchy in multicriteria decision analysis
Authors: Sironen Susanna , Kangas Jyrki , Leskinen Pekka
Published: December 2019

The main aim of this study is to propose applicable and easily adopted statistical analyses to restructure a sound multilevel decision hierarchy, which reflects decision makers' priorities, achieves a good balance between completeness and conciseness, and takes unconsciously intercorrelated subcriteria into account. A forest planning case was used as a numerical example to demonstrate the role of correlations, and the set‐up was based on the analytic hierarchy process (AHP). With the AHP, as well as other hierarchical multicriteria approaches, shape of the hierarchy structure may influence the decision makers and their judgments. In particular, the risk of overrating some main criteria exists, if the same concept is measured within multiple main criteria. We propose an approach, in which the subcriteria are grouped so that correlations between the different subcriteria are taken into account. A new decision hierarchy is constructed based on distance metrics, explanatory factor analysis, and cluster analysis. According the results, all these subsequent analyses supported each other. The tested methods seemed to be advisable tools to reveal the impacts of intercorrelated criteria and to guide the reconstructing a new decision hierarchy without intercorrelated subcriteria underneath main criteria.
Identification of a novel missense mutation in NIPAL4 gene: First 3D model construction predicted its pathogenicity
Authors: Laadhar Sahar , Ben Mansour Riadh , Marrakchi Slaheddine , Miled Nabil , Ennouri Mariem , Fischer Judith , Kaddechi Mohamed Ali , Turki Hamida , Fakhfakh Faiza
Published: December 2019

Background

The NIPAL4 gene is described to be implicated of Congenital Ichthyosiform Erythroderma (CIE). It encodes a magnesium transporter membrane‐associated protein, hypothetically involved in epidermal lipid processing and in lamellar body formation. The aim of this work is to investigate the causative mutation in a consanguineous Tunisian family with a clinical feature of CIE with a yellowish severe palmoplantar keratoderma.

Methods

Four patients were dignosed with CIE. The blood samples were collected from patients and all members of their nuclear family for mutation analysis. The novel mutation of NIPAL4 gene was analysed with several software tools to predict its pathogenicity. Then, the secondary structure and the 3D model of ichthyn was generated in silico.

Results

The sequencing analysis of the NIPAL4 gene in patients revealed a novel homozygous missense mutation c.534A>C (p.E178D) in the exon 4. Bioinformatic tools predicted its pathogenicity. The secondary structure prediction and the 3D model construction expected the presence of 9 transmembrane helices and revealed that mutation p.E178D was located in the middle of the second transmembrane helices. Besides, the 3D model construction revealed that the p.E178D mutation is inducing a shrinking in the transport channel containing the mutated NIPA4 protein.

Conclusion

We found a homozygous mutation in exon 4 of NIPAL4 c.534A>C (p.E178D), which was identified for the first time in our study. Bioinformatic investigations supported its involvement in the phenotype of patients with CIE. Interestingly, this mutation was located in the hypothetical transport channel cavity and leads to changes in the channel architecture, which would probably affect its transport function.
Fast contour propagation for MR‐guided prostate radiotherapy using convolutional neural networks
Authors: Eppenhof K.A.J. , Maspero M. , Savenije M.H.F. , de Boer J.C.J. , van der Voort van Zyp J.R.N. , Raaymakers B.W. , Raaijmakers A.J.E. , Veta M. , van den Berg C.A.T. , Pluim J.P.W.
Published: December 2019

Purpose

To quickly and automatically propagate organ contours from pretreatment to fraction images in magnetic resonance (MR)‐guided prostate external‐beam radiotherapy.

Methods

Five prostate cancer patients underwent 20 fractions of image‐guided external‐beam radiotherapy on a 1.5 T MR‐Linac system. For each patient, a pretreatment T2‐weighted three‐dimensional (3D) MR imaging (MRI) scan was used to delineate the clinical target volume (CTV) contours. The same scan was repeated during each fraction, with the CTV contour being manually adapted if necessary. A convolutional neural network (CNN) was trained for combined image registration and contour propagation. The network estimated the propagated contour and a deformation field between the two input images. The training set consisted of a synthetically generated ground truth of randomly deformed images and prostate segmentations. We performed a leave‐one‐out cross‐validation on the five patients and propagated the prostate segmentations from the pretreatment to the fraction scans. Three variants of the CNN, aimed at investigating supervision based on optimizing segmentation overlap, optimizing the registration, and a combination of the two were compared to results of the open‐source deformable registration software package Elastix.

Results

The neural networks trained on segmentation overlap or the combined objective achieved significantly better Hausdorff distances between predicted and ground truth contours than Elastix, at the much faster registration speed of 0.5 s. The CNN variant trained to optimize both the prostate overlap and deformation field, and the variant trained to only maximize the prostate overlap, produced the best propagation results.

Conclusions

A CNN trained on maximizing prostate overlap and minimizing registration errors provides a fast and accurate method for deformable contour propagation for prostate MR‐guided radiotherapy.
Spontaneous continuous motor unit single discharges
Authors: Posa Andreas , Niśkiewicz Izabela , Raescu Valerian , Emmer Alexander , Surov Alexey , Kornhuber Malte
Published: December 2019

Introduction

Motor unit hyperexcitability (MUH) may become manifest in needle electromyography (EMG) recordings as fasciculation potentials, myokymic discharges, or neuromyotonic discharges. Here, we describe a further MUH phenomenon.

Methods

Needle EMG recordings of the Neurology Hospital of Halle (Saale) stored in a video mode as .wav data between 2000 and 2015 were screened for spontaneous continuous motor unit single discharges (SCMUSD).

Results

We identified 23 video needle EMG waveforms from 14 patients with SCMUSD. The corresponding motor units discharged at a rate of about 6 H Z (6.3 ± 4.0; range, 1.3‐18.1). The coefficient of variation of the discharge rate was 3.5% ± 1.7%. Neurogenic disorders were diagnosed in 12 patients, limb girdle muscle dystrophy was diagnosed in one patient, and stiff‐limb syndrome was diagnosed in one patient.

Discussion

Spontaneous continuous motor unit single discharge, as described here, widens the spectrum of MUH phenomena.
Low‐dose rituximab every 6 months for the treatment of acetylcholine receptor–positive refractory generalized myasthenia gravis
Authors: Lu Jun , Zhong Huahua , Jing Sisi , Wang Liang , Xi Jianying , Lu Jiahong , Zhou Lei , Zhao Chongbo
Published: December 2019

Introduction

In this prospective, open‐label study we explore the effectiveness of low‐dose rituximab every 6 months in treating refractory generalized myasthenia gravis (GMG).

Methods

Twelve patients with acetylcholine receptor (AChR)‐positive refractory GMG were enrolled for the study. The primary endpoint was the change in quantitative myasthenia gravis (QMG) score from baseline to the study end. Secondary endpoints included changes in manual muscle testing (MMT), MG‐Related Activities of Daily Living (MG‐ADL), and 15‐item Quality‐of‐Life (MGQOL‐15) scores, as well as prednisolone reduction.

Results

MG decreased from 18.25 ± 4.03 to 8.42 ± 3.99 (P = .0001), MMT from 27.50 ± 17.78 to 4.58 ± 4.34 (P = .0001), ADL from 8.50 ± 2.84 to 1.17 ± 1.27 (P < .0001), MGQOL‐15 from 37.25 ± 13.78 to 17.50 ± 9.73 (P = .0015), and prednisolone dose from 29.38 ± 11.92 mg/day to 8.86 ± 1.88 mg/day (P ≤ .01).

Discussion

Low‐dose rituximab every 6 months is effective in treating refractory GMG patients.
Correlation of neutrophil/lymphocyte and platelet/lymphocyte ratios with the severity of idiopathic carpal tunnel syndrome
Authors: Güneş Muzaffer , Büyükgöl Hüseyin
Published: December 2019

Background

The aim of the present study was to investigate the correlation of the neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio with the severity of idiopathic carpal tunnel syndrome (CTS).

Methods

A total of 407 patients with idiopathic CTS (neurophysiologically 150 mild, 144 moderate, and 113 severe) and 206 subjects without CTS were included (control group).

Results

There was a positive correlation between the severity of CTS and NLR (r = 0.224; P < 0.001), age (r = 0.333; P < 0.001), and body mass index (r = 0.251; P < 0.001). A 1‐unit increase in NLR level was associated with an approximately 1.7‐fold higher incidence of CTS (P = 0.002; odds ratio = 1.668; 95% confidence interval = 1.199‐2.319).

Conclusions

Our results suggest that neurophysiologically more severe CTS is associated with higher NLR levels. The role of systemic inflammation in CTS should be investigated in further studies.
Metabolomic Profiles of Overweight/Obesity Phenotypes During Adolescence: A Cross‐Sectional Study in Project Viva
Authors: Perng Wei , Rifas‐Shiman Sheryl L. , Sordillo Joanne , Hivert Marie‐France , Oken Emily
Published: December 2019

Objective

The purpose of this article is to characterize metabolomic profiles of four overweight/obesity (OWOB) and metabolic risk (MetRisk) phenotypes among 524 adolescents aged approximately 13 years.

Methods

A four‐level phenotype variable (non‐OWOB and low MetRisk, non‐OWOB and high MetRisk, OWOB and low MetRisk, and OWOB and high MetRisk) was created using BMI percentile to define OWOB, and high versus low MetRisk was derived as the fourth versus first to third quartiles of a z score calculated as the average of five externally standardized z scores for waist circumference, homeostatic model assessment of insulin resistance, high‐density lipoprotein, triglycerides, and systolic blood pressure. Then associations of nine metabolite patterns derived from principal components analysis with phenotype after accounting for age, sex, race, and pubertal status were evaluated.

Results

Five metabolite patterns differed with respect to phenotype: factor 1 consisted of long‐chain fatty acids and was lower among non‐OWOB and high MetRisk (−0.90 [95% CI: −1.39 to −0.42]) versus non‐OWOB and low MetRisk (referent); factors 5 (branched‐chain amino acids), 8 (diacylglycerols), and 9 (steroid hormones) were highest among OWOB and high MetRisk; and factor 7 (long‐chain acylcarnitines) was higher among non‐OWOB and high MetRisk (0.47 [95% CI: 0.04 to 0.91]) and lower among OWOB and low MetRisk (−0.36 [95% CI: −0.68 to −0.04]).

Conclusions

Long‐chain fatty acids, branched‐chain amino acids, acylcarnitines, diacylglycerols, and steroid hormones differed by weight status and metabolic phenotype.
Association of Sleep Duration with Weight Gain and General and Central Obesity Risk in Chinese Adults: A Prospective Study
Authors: Ning Xuejuan , Lv Jun , Guo Yu , Bian Zheng , Tan Yunlong , Pei Pei , Chen Junshi , Yan Shichuan , Li Huimei , Fu Zhifang , Chen Yiping , Du Huaidong , Chen Zhengming , Yu Canqing , Li Liming ,   for the China Kadoorie Biobank (CKB) Collaborative Group
Published: December 2019

Objective

Evidence on the association between sleep duration and obesity among adults is inconsistent. Prospective studies investigating the association in Chinese adults have been limited. This study aims to prospectively evaluate sleep duration in relation to subsequent weight gain and general and central obesity risk among Chinese adults.

Methods

A total of 21,958 participants aged 30 to 79 years reported their daily sleep duration. Obesity indicators were objectively measured; then significant weight gain (≥ 5 kg) and general and central obesity were modeled as the outcome. Logistic regression models were used to estimate odds ratios and 95% CIs.

Results

Average sleep duration was 7.5 hours at baseline. During 8.0 ± 0.8 years of follow‐up, participants who reported sleeping ≤ 6 hours had higher risk for significant weight gain than those who slept 7 hours (multivariable‐adjusted odds ratio: 1.13; 95% CI: 1.02‐1.29). The association was stronger among those who were physically inactive at baseline (P = 0.04 for interaction). Short sleep duration was also associated with subsequent incident central obesity, with odds ratio of 1.13 (95% CI: 1.00‐1.28), but not with incident general obesity (P = 0.31).

Conclusions

Compared with those who slept 7 hours per day, short sleepers had an increased risk of significant weight gain and central obesity.
The effect of 3D printing on the morphological and mechanical properties of polycaprolactone filament and scaffold
Authors: Soufivand Anahita Ahmadi , Abolfathi Nabiollah , Hashemi Ata , Lee Sang Jin
Published: December 2019

Three‐dimensional (3D) printing becomes an attractive technique to fabricate tissue engineering scaffolds through its high control on fabrication and repeatability using the printing parameters. This technique can be combined by the finite element method (FEM), and tissue‐specific scaffolds with desirable morphological and mechanical properties can be designed and manufactured. In this study, the influential 3D printing parameters on the morphological and mechanical properties of polycaprolactone (PCL) filament and scaffold were studied experimentally and numerically. First, the effects of printing parameters and process on the properties of extruded PCL filament were investigated. Then, using FEM, the effects of filament specifications on the overall characteristics of the scaffold were evaluated. Results showed that both the printing process in terms of resting time and remaining time and the printing parameters like pressure, printing speed, and printing path length have influenced the filament properties. In addition, both the filament diameter and elastic modulus had significant effects on the properties of scaffold especially, a 20% increase in the filament diameter caused the scaffold compressive elastic modulus to rise by around 72%. It is concluded that the printing parameters and process must be tuned very well in fabricating scaffolds with the desired morphology and mechanical property.
Loss of GATA4 causes ectopic pancreas in the stomach
Authors: Rodríguez‐Seguel Elisa , Villamayor Laura , Arroyo Noelia , De Andrés Mónica P , Real Francisco X , Martín Franz , Cano David A , Rojas Anabel
Published: December 2019

Pancreatic heterotopia is defined as pancreatic tissue outside its normal location in the body and anatomically separated from the pancreas. In this work we have analyzed the stomach glandular epithelium of Gata4
flox/flox; Pdx1‐Cre mice (Gata4KO mice). We found that Gata4KO glandular epithelium displays an atypical morphology similar to the cornified squamous epithelium and exhibits upregulation of forestomach markers. The developing gastric units fail to form properly, and the glandular epithelial cells do not express markers of gastric gland in the absence of GATA4. Of interest, the developing glands of the Gata4KO stomach express pancreatic cell markers. Furthermore, a mass of pancreatic tissue located in the subserosa of the Gata4KO stomach is observed at adult stages. Heterotopic pancreas found in Gata4‐deficient mice contains all three pancreatic cell lineages: ductal, acinar, and endocrine. Moreover, Gata4 expression is downregulated in ectopic pancreatic tissue of some human biopsy samples. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.