bluuebunny/crossref_metadata_2025_split huggingface dataset:
The European medical information framework: A novel ecosystem for sharing healthcare data across Europe
Authors: Lovestone Simon ,   EMIF Consortium
Published: December 2019

AbstractIntroductionThe 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).MethodsThe 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.ResultsCurrently 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.ConclusionsEMIF 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

AbstractThe 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

AbstractBackgroundThe 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.MethodsFour 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.ResultsThe 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.ConclusionWe 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

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

AbstractIntroductionMotor 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.MethodsNeedle 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).ResultsWe 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.DiscussionSpontaneous 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

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

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

ObjectiveThe 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.MethodsA 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.ResultsFive 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]).ConclusionsLong‐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

ObjectiveEvidence 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.MethodsA 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.ResultsAverage 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).ConclusionsCompared with those who slept 7 hours per day, short sleepers had an increased risk of significant weight gain and central obesity.
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

AbstractPancreatic 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.
Early development of decreased β‐cell insulin secretion in children and adolescents with hemoglobin H disease and its relationship with levels of anemia
Authors: Nakavachara Pairunyar , Kajchamaporn Worarat , Pooliam Julaporn , Viprakasit Vip 
Published: December 2019

AbstractBackgroundDiabetes mellitus (DM) associated with iron overload has been reported among adults with transfusion‐dependent thalassemia and those with non‐transfusion‐dependent thalassemia (NTDT), especially in β‐thalassemia disease. However, little is known about glucose metabolism and how early its dysregulation can develop in α‐thalassemia hemoglobin H (Hb H) disease, which is one of the most common types of NTDT worldwide.ProcedureWe prospectively calculated glucose metabolism index in 40 patients (aged 10–25 years) with Hb H disease. Glucose metabolism data were compared between patients with deletional versus nondeletional Hb H, and between patients with normal versus abnormal insulin secretion/sensitivity.ResultsDespite normal glucose tolerance in all patients, 52.5% had abnormal insulinogenic index indicating decreased β‐cell insulin secretion. Patients with functional hemoglobin < 8 g/dL had significantly higher percentages of abnormal insulinogenic index. There was no significant difference in abnormal insulinogenic index between deletional and nondeletional Hb H.ConclusionDecreased β‐cell insulin secretion is highly prevalent among children and adolescents with Hb H disease, and it is associated with levels of functional anemia at baseline, but not with the type of Hb H disease. This result warrants heightened awareness among hematologists due to potentially increased risk of DM later in life.
Catheter‐directed thrombolysis for submassive pulmonary embolism in children: A case series
Authors: Belsky Jennifer , Warren Patrick , Stanek Joseph , Kumar Riten 
Published: December 2019

AbstractIncidence of venous thromboembolism, including pulmonary embolism (PE), continues to rise in children. Optimum management of submassive PE is unclear. The principal objective of this retrospective study was to investigate the radiological and clinical outcomes in children with submassive PE treated with catheter‐directed thrombolysis (CDT). Five patients underwent six episodes of CDT. No patient developed major/clinically relevant non‐major bleeding. Most patients had complete radiological thrombus resolution and no patient had evidence of chronic thromboembolic pulmonary hypertension. There is an urgent need for larger prospective cohort studies/randomized controlled trials to investigate the role of CDT in pediatric PE.
A survey of clarithromycin monotherapy and long‐term administration of ethambutol for patients with MAC lung disease in Japan: A retrospective cohort study using the database of health insurance claims
Authors: Iwao Tomohide , Kato Genta , Ito Isao , Aramaki Eiji , Kuroda Tomohiro 
Published: December 2019

AbstractBackgroundThe number of patients with nontuberculous mycobacteriosis (NTM) has increased exponentially in recent years. In Japan, approximately 88.8% of patients with NTM suffer from Mycobacterium avium‐intracellulare complex (MAC) lung disease. Incidence of MAC lung disease is increasing in particularly among the middle‐aged and elderly women owing to a rapid increase in nontuberculous mycobacterial infections.General treatment for MAC lung disease is chemotherapy. The type of chemotherapy recommended by specialists to prevent the development of a drug‐resistant strain of the bacteria consists of a combination of clarithromycin (CAM), rifampicin, and ethambutol (EB). CAM monotherapy is contraindicated by specialists owing to its high potential to induce drug‐resistant bacterial strains in patients with MAC lung disease. In addition, administering EB at doses not less than 1000 mg d−1 is not recommended to avoid adverse drug reactions. However, it is unclear how much such treatment cases exist in real world clinical settings. This is because no long‐term investigation has been carried out.Materials and MethodsThis study investigated treatment with these drugs from 2005 to 2017, by studying 1135 patients with MAC lung disease based on health insurance claims database.ResultsResults showed that approximately 9.2% (101 cases) were prescribed long‐term CAM monotherapy for 3 months or longer and approximately 3.6% (18 cases) were prescribed high doses of EB.ConclusionCAM monotherapy over a long period of time is potentially detrimental to some patients. Better awareness of the types of treatments and their potential negative effects will be beneficial to clinical practitioners.
Buying better biosecurity: Plant‐buying behaviour and the implications for an accreditation scheme in the horticultural sector
Authors: Dunn Mike , Marzano Mariella , Forster Jack 
Published: December 2019

Societal Impact StatementThe horticultural trade relies on healthy plants to flourish. However, its very nature means that it is also a key pathway for the introduction and spread of plant pests and diseases. These pests and diseases threaten horticultural stakeholders, and can also cause huge ecological and economic damage. A horticultural sector accreditation scheme, underpinned by best biosecurity practice, could help reduce these threats. Drawing on survey responses, this study examines the plant‐buying habits of UK consumers and their appetite for a horticulture accreditation scheme. We consider the necessary scope of such a scheme and outline how it could be made appealing to the plant‐buying public.
Summary

Movement of live plant material through the horticultural trade is a recurrent pathway for the introduction and spread of pests and diseases. An accreditation scheme underpinned by best biosecurity practice represents one approach to mitigating this risk. This research aims to determine whether an accreditation scheme would likely be supported by the public in the United Kingdom—a factor which would heavily influence its establishment and impact.

Consumer attitudes and behaviours were elicited through a survey of the UK's plant‐buying public (n = 1,500). The survey explored awareness of pests and diseases, the importance of biosecurity when making plant‐buying decisions (relative to other factors), and appetite for accredited products, including plants.

The sample exhibited limited awareness of plant pests and diseases and ascribed little importance to biosecurity during plant‐buying decisions. Instead, these decisions are influenced by “quality”—a factor also cited to explain consumers’ selection of (non‐horticultural) accredited goods over unaccredited varieties. Despite apparent support of a horticultural accreditation scheme's ideals, consumers expressed concern that accreditation could lead to more expensive products.

Public support for a scheme aiming to safeguard the wider environment from pests and diseases is unlikely to materialize without dedicated efforts to raise awareness by key influencers such as retailers. However, an assurance of high‐quality, healthy plants would increase a scheme's appeal. Furthermore, given the diversity of sources from which plants are obtained, any would‐be scheme must encompass a range of growers and sellers if it is to be widely considered by the plant‐buying public.