bluuebunny/crossref_metadata_2025_split huggingface dataset:
Therapy with cladribine is efficient and safe in patients previously treated with natalizumab
Authors: Möhn Nora , Skripuletz Thomas , Sühs Kurt-Wolfram , Menck Sylvia , Voß Elke , Stangel Martin 
Published: December 2019

Background: The humanized anti-α4 integrin monoclonal antibody natalizumab has proven to be very effective in patients with highly active relapsing-remitting multiple sclerosis (MS), but harbors the risk of progressive multifocal leukoencephalopathy (PML). Recently, new therapeutic options have become available for patients with high risk of developing PML while on natalizumab treatment. One of these new therapeutics is the oral synthetic purine analogue cladribine. In order to determine whether therapy with cladribine is effective and safe in patients with MS who previously had been treated with natalizumab, we analyzed clinical, radiological, and laboratory data of 17 patients whose disease modifying treatment (DMT) was switched from natalizumab to cladribine. Methods: A total of 17 patients with prior natalizumab treatment were switched to a DMT with cladribine because of a John Cunningham virus (JCV) antibody index above 1.5 ( N = 13), ongoing disease activity ( N = 6), magnetic resonance imaging (MRI) disease activity ( N = 4), or patients preference ( N = 2). A chart review and follow up of those patients was performed. In addition to MRI and laboratory data, clinical data regarding MS relapses and disease progression or possible adverse events were analyzed. Results: The median duration of cladribine treatment between February 2018 and April 2019 amounted to 9.7 months (range: 1.5–15 months). None of our 17 patients presented with a clinical relapse. Only two patients showed a new T2 lesion on brain MRI, but without any signs of PML. As expected, reduction of lymphocyte count was frequent in cladribine-treated patients, but only four patients exhibited lymphopenia grade 2 (500–800/µl). Conclusions: In our cohort the switch from natalizumab to cladribine treatment was effective and safe. So far, no serious adverse events other than lymphopenia have been observed, especially no cases of PML.
Sterilization of Drug-Loaded Composite Coatings for Implantable Glucose Biosensors
Authors: Tipnis Namita , Kastellorizios Michail , Legassey Allen , Papadimitrakopoulos Fotios , Jain Faquir , Burgess Diane J. 
Published: December 2019

Background: An anti-inflammatory drug-loaded composite coating (dexamethasone-loaded poly (lactic-co-glycolic acid) [PLGA] microspheres/polyvinyl alcohol [PVA] hydrogel) was previously developed to counter the foreign body reaction to a fully implantable continuous glucose monitoring biosensor. The long-term sensor functionality was ensured in the presence of the drug-loaded composite coating thus facilitating better diabetes control and management. In order to advance such a drug-device combination product toward clinical testing, addressing sterilization remains a key step due to the heterogeneity of the product components. The main objective of this research was to investigate the effect of two terminal sterilization techniques: gamma radiation and ethylene oxide (EO) on the stability of the anti-inflammatory coatings as well as retention of the glucose sensing ability of the implantable sensor. Method: The composite coatings, their individual components, and the glucose-sensing elements of the biosensor were subjected to low-temperature gamma radiation and EO cycles. Detailed characterization was conducted on all components before and after sterilization. Results: Exposure to gamma radiation affected dexamethasone crystallinity and glucose response linearity of the sensing element, whereas physical aging of microspheres in composite coatings was observed poststerilization with EO. Despite these effects, dexamethasone drug release from coatings was not significantly affected by either technique. Conclusion: The research findings indicate that both sterilization techniques are feasible for the sterilization of the dexamethasone-loaded PLGA microspheres/PVA hydrogel composite coatings, while EO was preferred for the sterilization of the glucose-sensing element of the biosensor.
Impaired compensatory hyperinsulinemia among nonobese type 2 diabetes patients: a cross-sectional study
Authors: Sarkar Jit , Maity Sujay Krishna , Sen Abhishek , Nargis Titli , Ray Dipika , Chakrabarti Partha 
Published: December 2019

Aims: Obesity associated prolonged hyperinsulinemia followed by β-cell failure is well established as the pathology behind type 2 diabetes mellitus (T2DM). However, studies on nonobese T2DM have reported it to be a distinct clinical entity with predominant insulin secretory defect. We, therefore, hypothesized that compensatory hyperinsulinemia in response to weight gain is impaired in nonobese subjects. Methods: This was a cross-sectional study from a community-based metabolic health screening program. Adiposity parameters including body mass index (BMI), waist circumference (WC), body fat percentage, plasma leptin concentration and metabolic parameters namely fasting insulin, glucose, total cholesterol, and triglycerides were measured in 650 individuals (73% healthy, 62% nonobese with a BMI <25). Results: In contrast to obese T2DM, nonobese T2DM patients did not exhibit significant hyperinsulinemia compared with the nonobese healthy group. Age, sex, and fasting glucose adjusted insulin levels, homeostatic model assessment of insulin resistance (HOMA-IR) and HOMA-beta cell function (HOMA-B) were increased in obese T2DM compared with nonobese T2DM. Although adiposity parameters showed strong correlation with fasting insulin in obese healthy ( r = 0.38, 0.38, and 0.42, respectively; all p values < 0.001) and T2DM ( r = 0.54, 0.54, and 0.66, respectively; all p < 0.001), only BMI and leptin showed a weak correlation with insulin in the nonobese healthy group (0.13 and 0.13, respectively; all p < 0.05) which were completely lost in the nonobese T2DM. Conclusions: Compensatory hyperinsulinemia in response to weight gain is impaired in the nonobese population making insulin secretory defect rather than IR the major pathology behind nonobese T2DM.
Home-based exercise with telemonitoring guidance in patients with coronary artery disease: Does it improve long-term physical fitness?
Authors: Avila Andrea , Claes Jomme , Buys Roselien , Azzawi May , Vanhees Luc , Cornelissen Veronique 
Published: December 2019

Background Home-based interventions might facilitate the lifelong uptake of a physically active lifestyle following completion of a supervised phase II exercise-based cardiac rehabilitation. Yet, data on the long-term effectiveness of home-based exercise training on physical activity and exercise capacity are scarce. Objective The purpose of the TeleRehabilitation in Coronary Heart disease (TRiCH) study was to compare the long-term effects of a short home-based phase III exercise programme with telemonitoring guidance to a prolonged centre-based phase III programme in coronary artery disease patients. The primary outcome was exercise capacity. Secondary outcomes included physical activity behaviour, cardiovascular risk profile and health-related quality of life. Methods Ninety coronary artery disease patients (80 men) were randomly assigned to 3 months of home-based (30), centre-based (30) or a control group (30) on a 1:1:1 basis after completion of their phase II ambulatory cardiac rehabilitation programme. Outcome measures were assessed at discharge of the phase II programme and after one year. Results Eighty patients (72 (91%) men; mean age 62.6 years) completed the one-year follow-up measurements. Exercise capacity and secondary outcomes were preserved in all three groups ( Ptime > 0.05 for all), irrespective of the intervention ( Pinteraction > 0.05 for all). Eighty-five per cent of patients met the international guidelines for physical activity ( Ptime < 0.05). No interaction effect was found for physical activity. Conclusion Overall, exercise capacity remained stable during one year following phase II cardiac rehabilitation. Our home-based exercise intervention was as effective as centre-based and did not result in higher levels of exercise capacity and physical activity compared to the other two interventions. Trial registration ClinicalTrials.gov NCT02047942. https://clinicaltrials.gov/ct2/show/NCT02047942
Bioethics Education in the Medical Programme among Malaysian Medical Schools: Where Are We Now?
Authors: Sim Joong Hiong , Ngan Olivia Miu Yung , Ng Ho Keung 
Published: December 2019

Introduction: A global trend in medical education is the inclusion of bioethics teaching in medical programme. The objective of this article is to describe the current state of bioethics education in the medical programme among Malaysian medical schools. Method: A national survey was conducted among Malaysian medical schools between January and March 2019. One representative from each medical school was invited to respond to the survey. Respondents were faculty members involved in teaching and assessment of bioethics in their medical schools, or/and in developing and coordinating bioethics curriculum. Descriptive statistics were reported. Findings: Out of 30 medical schools, 11 completed and returned the survey (overall response rate = 36.7%). Of these 11 schools, 6/10 (60%) were from public institutions while 5/20 (25%) were from private institutions. All except 1 school implemented a formal bioethics curriculum. A wide range of bioethics topics are currently taught in the medical programme. The majority involved in teaching bioethics were health care professionals (mainly clinicians), followed by lawyers. Lecture and attendance, respectively, are the most common teaching and assessment method. Major barriers to the implementation of bioethics education included limited qualified teaching staff (6/11 = 54.5%), no established curriculum to follow (5/11 = 45.5%), limited financial resources to hire qualified staff (4/11 = 36.4%), and no consensus among faculty members (4/11 = 36.4%). Conclusion: Bioethics education in Malaysia is relatively new and mostly limited by a shortage of scholars in bioethics. National support and institutional collaboration in providing bioethics training is the key to enhance the quality of bioethics education.
Medical empirical research on forest bathing (Shinrin-yoku): a systematic review
Authors: Wen Ye , Yan Qi , Pan Yangliu , Gu Xinren , Liu Yuanqiu 
Published: December 2019

Abstract
Aims
This study focused on the newest evidence of the relationship between forest environmental exposure and human health and assessed the health efficacy of forest bathing on the human body as well as the methodological quality of a single study, aiming to provide scientific guidance for interdisciplinary integration of forestry and medicine.

Method
Through PubMed, Embase, and Cochrane Library, 210 papers from January 1, 2015, to April 1, 2019, were retrieved, and the final 28 papers meeting the inclusion criteria were included in the study.

Result
The methodological quality of papers included in the study was assessed quantitatively with the Downs and Black checklist. The methodological quality of papers using randomized controlled trials is significantly higher than that of papers using non-randomized controlled trials (p < 0.05). Papers included in the study were analyzed qualitatively. The results demonstrated that forest bathing activities might have the following merits: remarkably improving cardiovascular function, hemodynamic indexes, neuroendocrine indexes, metabolic indexes, immunity and inflammatory indexes, antioxidant indexes, and electrophysiological indexes; significantly enhancing people’s emotional state, attitude, and feelings towards things, physical and psychological recovery, and adaptive behaviors; and obvious alleviation of anxiety and depression.

Conclusion
Forest bathing activities may significantly improve people’s physical and psychological health. In the future, medical empirical studies of forest bathing should reinforce basic studies and interdisciplinary exchange to enhance the methodological quality of papers while decreasing the risk of bias, thereby raising the grade of paper evidence.
Gamma-glutamyl transpeptidase (γ-GTP) has an ambivalent association with hypertension and atherosclerosis among elderly Japanese men: a cross-sectional study
Authors: Shimizu Yuji , Kawashiri Shin-Ya , Kiyoura Kairi , Nobusue Kenichi , Yamanashi Hirotomo , Nagata Yasuhiro , Maeda Takahiro 
Published: December 2019

Abstract
Background
Even though there is bidirectional association between hypertension and atherosclerosis, atherosclerosis itself is involved in the process of endothelial repair. To clarify the association of endothelial repair with hypertension, a cross-sectional study was conducted.

Methods
We conducted a cross-sectional study of 562 elderly Japanese men aged 60–69. As gamma-glutamyl transpeptidase (γ-GTP) could act as a marker of oxidative stress that injures endothelial cell and higher levels of CD34-positive cell indicate a higher activity of endothelial repair, we therefore performed a CD34-positive level specific analysis of γ-GTP on atherosclerosis and hypertension.

Results
In the present study population, hypertension was independently and positively associated with atherosclerosis (multivariable odds ratio (OR) = 2.09 (1.30, 3.35)). Among participants with high CD34-positive cells, γ-GTP showed significant and positive association with atherosclerosis (OR of the log-transformed value of γ-GTP (OR) = 2.26 (1.32, 3.86)) but not with hypertension (OR = 0.77 (0.51, 1.17)). Among participants with low CD34-positive cells, even γ-GTP showed no significant association with atherosclerosis (OR = 0.92 (0.51, 1.68)), but was significantly and positively associated with hypertension (OR = 1.99 (1.27, 3.12)).

Conclusions
γ-GTP revealed to have ambivalent association with hypertension and atherosclerosis. Active endothelial repair that is associated with atherosclerosis might have beneficial association with hypertension.
Integrating protein localization with automated signaling pathway reconstruction
Authors: Youssef Ibrahim , Law Jeffrey , Ritz Anna 
Published: December 2019

Abstract
Background
Understanding cellular responses via signal transduction is a core focus in systems biology. Tools to automatically reconstruct signaling pathways from protein-protein interactions (PPIs) can help biologists generate testable hypotheses about signaling. However, automatic reconstruction of signaling pathways suffers from many interactions with the same confidence score leading to many equally good candidates. Further, some reconstructions are biologically misleading due to ignoring protein localization information.

Results
We propose LocPL, a method to improve the automatic reconstruction of signaling pathways from PPIs by incorporating information about protein localization in the reconstructions. The method relies on a dynamic program to ensure that the proteins in a reconstruction are localized in cellular compartments that are consistent with signal transduction from the membrane to the nucleus. LocPL and existing reconstruction algorithms are applied to two PPI networks and assessed using both global and local definitions of accuracy. LocPL produces more accurate and biologically meaningful reconstructions on a versatile set of signaling pathways.

Conclusion
LocPL is a powerful tool to automatically reconstruct signaling pathways from PPIs that leverages cellular localization information about proteins. The underlying dynamic program and signaling model are flexible enough to study cellular signaling under different settings of signaling flow across the cellular compartments.
A supervised term ranking model for diversity enhanced biomedical information retrieval
Authors: Xu Bo , Lin Hongfei , Yang Liang , Xu Kan , Zhang Yijia , Zhang Dongyu , Yang Zhihao , Wang Jian , Lin Yuan , Yin Fuliang 
Published: December 2019

AbstractBackgroundThe number of biomedical research articles have increased exponentially with the advancement of biomedicine in recent years. These articles have thus brought a great difficulty in obtaining the needed information of researchers. Information retrieval technologies seek to tackle the problem. However, information needs cannot be completely satisfied by directly introducing the existing information retrieval techniques. Therefore, biomedical information retrieval not only focuses on the relevance of search results, but also aims to promote the completeness of the results, which is referred as the diversity-oriented retrieval.ResultsWe address the diversity-oriented biomedical retrieval task using a supervised term ranking model. The model is learned through a supervised query expansion process for term refinement. Based on the model, the most relevant and diversified terms are selected to enrich the original query. The expanded query is then fed into a second retrieval to improve the relevance and diversity of search results. To this end, we propose three diversity-oriented optimization strategies in our model, including the diversified term labeling strategy, the biomedical resource-based term features and a diversity-oriented group sampling learning method. Experimental results on TREC Genomics collections demonstrate the effectiveness of the proposed model in improving the relevance and the diversity of search results.ConclusionsThe proposed three strategies jointly contribute to the improvement of biomedical retrieval performance. Our model yields more relevant and diversified results than the state-of-the-art baseline models. Moreover, our method provides a general framework for improving biomedical retrieval performance, and can be used as the basis for future work.
Predicting virus-host association by Kernelized logistic matrix factorization and similarity network fusion
Authors: Liu Dan , Ma Yingjun , Jiang Xingpeng , He Tingting 
Published: December 2019

Abstract
Background
Viruses are closely related to bacteria and human diseases. It is of great significance to predict associations between viruses and hosts for understanding the dynamics and complex functional networks in microbial community. With the rapid development of the metagenomics sequencing, some methods based on sequence similarity and genomic homology have been used to predict associations between viruses and hosts. However, the known virus-host association network was ignored in these methods.

Results
We proposed a kernelized logistic matrix factorization with integrating different information to predict potential virus-host associations on the heterogeneous network (ILMF-VH) which is constructed by connecting a virus network with a host network based on known virus-host associations. The virus network is constructed based on oligonucleotide frequency measurement, and the host network is constructed by integrating oligonucleotide frequency similarity and Gaussian interaction profile kernel similarity through similarity network fusion. The host prediction accuracy of our method is better than other methods. In addition, case studies show that the host of crAssphage predicted by ILMF-VH is consistent with presumed host in previous studies, and another potential host Escherichia coli is also predicted.

Conclusions
The proposed model is an effective computational tool for predicting interactions between viruses and hosts effectively, and it has great potential for discovering novel hosts of viruses.
3-Dimensional facial expression recognition in human using multi-points warping
Authors: Agbolade Olalekan , Nazri Azree , Yaakob Razali , Ghani Abdul Azim , Cheah Yoke Kqueen 
Published: December 2019

AbstractBackgroundExpression inH-sapiensplays a remarkable role when it comes to social communication. The identification of this expression by human beings is relatively easy and accurate. However, achieving the same result in 3D by machine remains a challenge in computer vision. This is due to the current challenges facing facial data acquisition in 3D; such as lack of homology and complex mathematical analysis for facial point digitization. This study proposes facial expression recognition in human with the application of Multi-points Warping for 3D facial landmark by building a template mesh as a reference object. This template mesh is thereby applied to each of the target mesh on Stirling/ESRC and Bosphorus datasets. The semi-landmarks are allowed to slide along tangents to the curves and surfaces until the bending energy between a template and a target form is minimal and localization error is assessed using Procrustes ANOVA. By using Principal Component Analysis (PCA) for feature selection, classification is done using Linear Discriminant Analysis (LDA).ResultThe localization error is validated on the two datasets with superior performance over the state-of-the-art methods and variation in the expression is visualized using Principal Components (PCs). The deformations show various expression regions in the faces. The results indicate that Sad expression has the lowest recognition accuracy on both datasets. The classifier achieved a recognition accuracy of 99.58 and 99.32% on Stirling/ESRC and Bosphorus, respectively.ConclusionThe results demonstrate that the method is robust and in agreement with the state-of-the-art results.
deltaRpkm: an R package for a rapid detection of differential gene presence between related bacterial genomes
Authors: Akarsu Hatice , Aguilar-Bultet Lisandra , Falquet Laurent 
Published: December 2019

Abstract
Background
Comparative genomics has seen the development of many software performing the clustering, polymorphism and gene content analysis of genomes at different phylogenetic levels (isolates, species). These tools rely on de novo assembly and/or multiple alignments that can be computationally intensive for large datasets. With a large number of similar genomes in particular, e.g., in surveillance and outbreak detection, assembling each genome can become a redundant and expensive step in the identification of genes potentially involved in a given clinical feature.

Results
We have developed deltaRpkm, an R package that performs a rapid differential gene presence evaluation between two large groups of closely related genomes. Starting from a standard gene count table, deltaRpkm computes the RPKM per gene per sample, then the inter-group δRPKM values, the corresponding median δRPKM (m) for each gene and the global standard deviation value of m (sm). Genes with m >  = 2 ∗ sm (standard deviation s of all the m values) are considered as “differentially present” in the reference genome group. Our simple yet effective method of differential RPKM has been successfully applied in a recent study published by our group (N = 225 genomes of Listeria monocytogenes) (Aguilar-Bultet et al. Front Cell Infect Microbiol 8:20, 2018).

Conclusions
To our knowledge, deltaRpkm is the first tool to propose a straightforward inter-group differential gene presence analysis with large datasets of related genomes, including non-coding genes, and to output directly a list of genes potentially involved in a phenotype.