bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of drug-related problems among type 2 diabetic patients on follow up at Hiwot Fana Specialized University Hospital, Harar, Eastern Ethiopia
Authors: Abdulmalik Haymen , Tadiwos Yohannes , Legese Nanati 
Published: November 2019

Abstract
Objectives
To assess the drug-related problem among patients with type 2 diabetes at Hiwot Fana Specialized University Hospital.

Results
In this study, a total of 148 patient medication records were included. More than half, 83 (57.4%) were men and the rest 65 (42.6%) were women. The mean age of the study participants was 51.26 ± 7.08. Around one-third (74.3%) of the participants had urban residency. A total of 127 drug-related problems were identified, of which dosage too low was the most common type of DRP encountered, 46 (36.2%), followed by unnecessary drug therapy, 25 (19.7%) and ineffective drug therapy, 25 (19.7%). 95 (64.2%) of the patients had at least one drug-related problem. Among patients with DRP, more than half of them, 59 (62.1%) had a single DRP. Out of the total participants, 85 (57.4%) of them were taking one anti-diabetic medication and 63 (42.6%) of them dual anti-diabetic medications. Only half of the patients have attained the desired FBG level. There was no patient who had experienced more than two types of drug-related problems at a time. Less than 10% of patients were taking five or more drugs at a time.
Validation and characterisation of a DNA methylation alcohol biomarker across the life course
Authors: Yousefi Paul Darius , Richmond Rebecca , Langdon Ryan , Ness Andrew , Liu Chunyu , Levy Daniel , Relton Caroline , Suderman Matthew , Zuccolo Luisa 
Published: November 2019

Abstract
Background
Recently, an alcohol predictor was developed using DNA methylation at 144 CpG sites (DNAm-Alc) as a biomarker for improved clinical or epidemiologic assessment of alcohol-related ill health. We validate the performance and characterise the drivers of this DNAm-Alc for the first time in independent populations.

Results
In N = 1049 parents from the Avon Longitudinal Study of Parents and Children (ALSPAC) Accessible Resource for Integrated Epigenomic Studies (ARIES) at midlife, we found DNAm-Alc explained 7.6% of the variation in alcohol intake, roughly half of what had been reported previously, and interestingly explained a larger 9.8% of Alcohol Use Disorders Identification Test (AUDIT) score, a scale of alcohol use disorder. Explanatory capacity in participants from the offspring generation of ARIES measured during adolescence was much lower. However, DNAm-Alc explained 14.3% of the variation in replication using the Head and Neck 5000 (HN5000) clinical cohort that had higher average alcohol consumption. To investigate whether this relationship was being driven by genetic and/or earlier environment confounding, we examined how earlier versus concurrent DNAm-Alc measures predicted AUDIT scores. In both ARIES parental and offspring generations, we observed associations between AUDIT and concurrent, but not earlier DNAm-Alc, suggesting independence from genetic and stable environmental contributions.

Conclusions
The stronger relationship between DNAm-Alcs and AUDIT in parents at midlife compared to adolescents despite similar levels of consumption suggests that DNAm-Alc likely reflects long-term patterns of alcohol abuse. Such biomarkers may have potential applications for biomonitoring and risk prediction, especially in cases where reporting bias is a concern.
Machine-learned analysis of global and glial/opioid intersection–related DNA methylation in patients with persistent pain after breast cancer surgery
Authors: Kringel Dario , Kaunisto Mari A. , Kalso Eija , Lötsch Jörn 
Published: November 2019

Abstract
Background
Glial cells in the central nervous system play a key role in neuroinflammation and subsequent central sensitization to pain. They are therefore involved in the development of persistent pain. One of the main sites of interaction of the immune system with persistent pain has been identified as neuro-immune crosstalk at the glial-opioid interface. The present study examined a potential association between the DNA methylation of two key players of glial/opioid intersection and persistent postoperative pain.

Methods
In a cohort of 140 women who had undergone breast cancer surgery, and were assigned based on a 3-year follow-up to either a persistent or non-persistent pain phenotype, the role of epigenetic regulation of key players in the glial-opioid interface was assessed. The methylation of genes coding for the Toll-like receptor 4 (TLR4) as a major mediator of glial contributions to persistent pain or for the μ-opioid receptor (OPRM1) was analyzed and its association with the pain phenotype was compared with that conferred by global genome-wide DNA methylation assessed via quantification of the methylation in the retrotransposon LINE1.

Results
Training of machine learning algorithms indicated that the global DNA methylation provided a similar diagnostic accuracy for persistent pain as previously established non-genetic predictors. However, the diagnosis can be based on a single DNA based marker. By contrast, the methylation of TLR4 or OPRM1 genes could not contribute further to the allocation of the patients to the pain-related phenotype groups.

Conclusions
While clearly supporting a predictive utility of epigenetic testing, the present analysis cannot provide support for specific epigenetic modulation of persistent postoperative pain via methylation of two key genes of the glial-opioid interface.
Electrical storm 11 days after acute myocardial infarction: a case report
Authors: Ohsawa Sayaka , Isono Hiroki , Ojima Eiji , Toyama Masahiro , Kuroda Yasuhisa , Watanabe Shigeyuki , Abe Toshikazu 
Published: November 2019

Abstract
Background
The definition of electrical storm is still debated. For example, an electrical storm is defined as a clustering of three or more separate episodes of ventricular tachycardia/ventricular fibrillation within 24 hours or one or more episodes occurring within 5 minutes of termination of the previous episode of ventricular tachycardia/ventricular fibrillation. When it is refractory to medications, prompt assessments by coronary angiography, sedation, and overdrive pacing should be performed. An electrical storm may occur anytime, including at night or after the patient leaves an intensive care unit.

Case presentation
A 70-year-old Japanese man with type 2 diabetes mellitus was diagnosed as having ST-elevation myocardial infarction. His clinical course after an urgent percutaneous coronary intervention was uneventful, but he developed electrical storm that was refractory to antiarrhythmic medications on day 11 of hospitalization. We used sedative medications and performed ventricular overdrive pacing and transferred him to a university hospital for further treatment, which included electrical ablation and cardioverter-defibrillator implantation.

Conclusion
An electrical storm is a relatively rare and fatal complication of acute myocardial infarction. It is important that the treatment choices for this condition are known by non-cardiologist physicians who might encounter this rare condition.
Fibroblast growth factor-2 stimulates proliferation of human adipose-derived stem cells via Src activation
Authors: Ma Yuanyuan , Kakudo Natsuko , Morimoto Naoki , Lai Fangyuan , Taketani Shigeru , Kusumoto Kenji 
Published: November 2019

Abstract
Background
Human adipose-derived stem cells (hASCs) are a subset of mesenchymal stem cells (MSCs); it has been regarded as one of the most promising stem cells. We previously found that fibroblast growth factor-2 (FGF-2) enhanced the proliferation and differentiation of hASC. However, the mechanisms involved in the growth of hASCs by FGF-2 have not been investigated.

Methods
Human adipose-derived stem cells (hASCs) were cultured with FGF-2, and cell growth was assessed. Effects of FGF Receptor (FGFR) inhibitor (NVP-BGJ398), ERK1/2 inhibitor (PD98059), PI3K/Akt inhibitor (LY294002), JNK inhibitor (SP600125), and p38 MAPK inhibitor (SB203580) and Src inhibitor (PP1) on the proliferation were investigated. At the same time, we assessed the effect of FGFR inhibitor on several signaling enzymes such as ERK1/2, JNK, p38, and Akt, in protein level. The involvement of Src activation by FGF-2 was also examined.

Results
FGF-2 markedly promoted proliferation of hASCs at concentrations lower than 10 ng/ml and stimulated cell progression to the S and G2/M phases. Proliferation was blocked by the FGFR inhibitor (NVP-BGJ398) and various signaling pathway inhibitors, such as Erk1/2 inhibitor (PD98059), PI3K/Akt inhibitor (LY294002), JNK inhibitor (SP600125), and p38MAPK inhibitor (SB203580). The FGFR inhibitor reduced the activation of protein kinases, such as AKT, Erk1/2, JNK, and p38, in several signaling pathways. The downstream kinase of FGFR, Src, was activated by FGF-2, and its activation was canceled by the FGFR inhibitor. MEK1/2, a downstream kinase of Src, was parallelly regulated by FGF-2. The Src inhibitor (PP1) markedly blocked the proliferation of hASCs via inhibition of Src and MEK1/2.

Conclusion
Src activation is indispensable for FGF-2-mediated proliferation of ASCs, as well as the subsequent activation of multi-signaling pathways.
The influence of biological sex and sex hormones on bile acid synthesis and cholesterol homeostasis
Authors: Phelps Taylor , Snyder Erin , Rodriguez Erin , Child Hailey , Harvey Pamela 
Published: November 2019

AbstractObesity and elevated serum lipids are associated with a threefold increase in the risk of developing atherosclerosis, a condition that underlies stroke, myocardial infarction, and sudden cardiac death. Strategies that aim to reduce serum cholesterol through modulation of liver enzymes have been successful in decreasing the risk of developing atherosclerosis and reducing mortality. Statins, which inhibit cholesterol biosynthesis in the liver, are considered among the most successful compounds developed for the treatment of cardiovascular disease. However, recent debate surrounding their effectiveness and safety prompts consideration of alternative cholesterol-lowering therapies, including increasing cholesterol catabolism through bile acid (BA) synthesis. Targeting the enzymes that convert cholesterol to BAs represents a promising alternative to other cholesterol-lowering approaches that treat atherosclerosis as well as fatty liver diseases and diabetes mellitus. Compounds that modify the activity of these pathways have been developed; however, there remains a lack of consideration of biological sex. This is necessary in light of strong evidence for sexual dimorphisms not only in the incidence and progression of the diseases they influence but also in the expression and activity of the proteins affected and in the manner in which men and women respond to drugs that modify lipid handling in the liver. A thorough understanding of the enzymes involved in cholesterol catabolism and modulation by biological sex is necessary to maximize their therapeutic potential.
ACID: a free tool for drug repurposing using consensus inverse docking strategy
Authors: Wang Fan , Wu Feng-Xu , Li Cheng-Zhang , Jia Chen-Yang , Su Sun-Wen , Hao Ge-Fei , Yang Guang-Fu 
Published: November 2019

AbstractDrug repurposing offers a promising alternative to dramatically shorten the process of traditional de novo development of a drug. These efforts leverage the fact that a single molecule can act on multiple targets and could be beneficial to indications where the additional targets are relevant. Hence, extensive research efforts have been directed toward developing drug based computational approaches. However, many drug based approaches are known to incur low successful rates, due to incomplete modeling of drug-target interactions. There are also many technical limitations to transform theoretical computational models into practical use. Drug based approaches may, thus, still face challenges for drug repurposing task. Upon this challenge, we developed a consensus inverse docking (CID) workflow, which has a ~ 10% enhancement in success rate compared with current best method. Besides, an easily accessible web server named auto in silico consensus inverse docking (ACID) was designed based on this workflow (http://chemyang.ccnu.edu.cn/ccb/server/ACID).
Short-term discontinuation of vagal nerve stimulation alters 18F-FDG blood pool activity: an exploratory interventional study in epilepsy patients
Authors: Boswijk Ellen , Franssen Renee , Vijgen Guy H. E. J. , Wierts Roel , van der Pol Jochem A. J. , Mingels Alma M. A. , Cornips Erwin M. J. , Majoie Marian H. J. M. , van Marken Lichtenbelt Wouter D. , Mottaghy Felix M. , Wildberger Joachim E. , Bucerius Jan 
Published: November 2019

Abstract
Background
Vagus nerve activation impacts inflammation. Therefore, we hypothesized that vagal nerve stimulation (VNS) influenced arterial wall inflammation as measured by 18F-FDG uptake.

Results
Ten patients with left-sided VNS for refractory epilepsy were studied during stimulation (VNS-on) and in the hours after stimulation was switched off (VNS-off). In nine patients, 18F-FDG uptake was measured in the right carotid artery, aorta, bone marrow, spleen, and adipose tissue. Target-to-background ratios (TBRs) were calculated to normalize the respective standardized uptake values (SUVs) for venous blood pool activity. Median values are shown with interquartile range and compared using the Wilcoxon signed-rank test. Arterial SUVs tended to be higher during VNS-off than VNS-on [SUVmax all vessels 1.8 (1.5–2.2) vs. 1.7 (1.2–2.0), p = 0.051]. However, a larger difference was found for the venous blood pool at this time point, reaching statistical significance in the vena cava superior [meanSUVmean 1.3 (1.1–1.4) vs. 1.0 (0.8–1.1); p = 0.011], resulting in non-significant lower arterial TBRs during VNS-off than VNS-on. Differences in the remaining tissues were not significant. Insulin levels increased after VNS was switched off [55.0 pmol/L (45.9–96.8) vs. 48.1 pmol/L (36.9–61.8); p = 0.047]. The concurrent increase in glucose levels was not statistically significant [4.8 mmol/L (4.7–5.3) vs. 4.6 mmol/L (4.5–5.2); p = 0.075].

Conclusions
Short-term discontinuation of VNS did not show a consistent change in arterial wall 18F-FDG-uptake. However, VNS did alter insulin and 18F-FDG blood levels, possibly as a result of sympathetic activation.
Brucella melitensis Rev.1 vaccination generates a higher shedding risk of the vaccine strain in Alpine ibex (Capra ibex) compared to the domestic goat (Capra hircus)
Authors: Ponsart Claire , Riou Mickaël , Locatelli Yann , Jacques Isabelle , Fadeau Alain , Jay Maryne , Simon Roland , Perrot Ludivine , Freddi Luca , Breton Sylvain , Chaumeil Thierry , Blanc Barbara , Ortiz Katia , Vion Colin , Rioult Damien , Quéméré Erwan , Sarradin Pierre , Chollet Jean-Yves , Garin-Bastuji Bruno , Rossi Sophie 
Published: November 2019

AbstractEpidemiological investigations implemented in wild and domestic ruminants evidenced a reservoir forBrucellainCapra ibexin the French Alps. Vaccination was considered as a possible way to controlBrucellainfection in this wildlife population. Twelve ibexes and twelve goats were allocated into four groups housed separately, each including six males or six non-pregnant females. Four to five animals were vaccinated and one or two animals were contact animals. Half of the animals were necropsied 45 days post-vaccination (pv), and the remaining ones at 90 days pv. Additional samples were collected 20 and 68 days pv to explore bacterial distribution in organs and humoral immunity. Neither clinical signs norBrucella-specific lesions were observed and all vaccinated animals seroconverted.Brucelladistribution and antibody profiles were highly contrasted between both species. Proportion of infected samples was significantly higher in ibex compared to goats and decreased between 45 and 90 days pv. Two male ibex presented urogenital excretion at 20 or 45 days pv. The bacterial load was higher 45 days in ibexes compared to goats, whereas it remained moderate to low 90 days pv in both species with large variability between animals. In this experiment, differences between species remained the main source of variation, with low impact of other individual factors. To conclude, multiplicative and shedding capacity of Rev.1 was much higher in ibex compared to goats within 90 days. These results provide initial information on the potential usein naturaof a commercial vaccine.
Nature and consequences of interactions between Salmonella enterica serovar Dublin and host cells in cattle
Authors: Vohra Prerna , Vrettou Christina , Hope Jayne C. , Hopkins John , Stevens Mark P. 
Published: November 2019

AbstractSalmonella entericais a veterinary and zoonotic pathogen of global importance. While murine and cell-based models of infection have provided considerable knowledge about the molecular basis of virulence ofSalmonella, relatively little is known about salmonellosis in naturally-affected large animal hosts such as cattle, which are a reservoir of human salmonellosis. As in humans,Salmonellacauses bovine disease ranging from self-limiting enteritis to systemic typhoid-like disease and exerts significant economic and welfare costs. Understanding the nature and consequences ofSalmonellainteractions with bovine cells will inform the design of effective vaccines and interventions to control animal and zoonotic infections. In calves challenged orally withS. Dublin expressing green fluorescent protein (GFP) we observed that the bacteria were predominantly extracellular in the distal ileal mucosa and within gut-associated lymph nodes 48 h post-infection. Intracellular bacteria, identified by flow cytometry using the GFP signal, were predominantly within MHCII+macrophage-like cells. In contrast to observations from murine models, theseS.Dublin-infected cells had elevated levels of MHCII and CD40 compared to both uninfected cells from the same tissue and cells from the cognate tissue of uninfected animals. Moreover, no gross changes of the architecture of infected lymph nodes were observed as was described previously in a mouse model. In order to further investigateSalmonella-macrophage interactions, net replication ofS. entericaserovars that differ in virulence in cattle was measured in bovine blood-derived macrophages by enumeration of gentamicin-protected bacteria and fluorescence dilution, but did not correlate with host-specificity.
Investment performance measurement of new generation mobile communication networks based on dynamic DEA model
Authors: Du Yu , Zhang Xiaohang , Li Zhengren , Wu Ling 
Published: November 2019

AbstractWith the fast development of the mobile internet in recent years, the new generation mobile communication networks as the basic supporting have received widespread attentions. During the upgrading period of new generation networks, the telecom operators need to grasp the network investment performance, which is one of the key factors for deploying the new generation networks and arranging new services effectively. In this paper, first, we propose a method based on the dynamic DEA model and the sensitivity analysis to measure the network investment performance of telecom operators, which gives the managers and researchers insight into the changing process of the key influence factors on the investment performance. Then, we build the input-output indicators system of the DEA model from five dimensions, such as INVESTMENT, SUPPLY, ADOPTION, USAGE, and REVENUE, for a more complete and valid characterization to the network investment performance. At last, we apply the proposed method to conduct an empirical research on the operational data of one Chinese telecom operator from 2013 to 2015, which has been the initial launch phase of 4G network. Based on the result, we develop effective investment strategies for the upgrading period of networks, which also gives guidelines for the investment of 5G and other new generation networks in the future.
Multi-cloud provisioning of business processes
Authors: Kritikos Kyriakos , Zeginis Chrysostomos , Iranzo Joaquin , Gonzalez Roman Sosa , Seybold Daniel , Griesinger Frank , Domaschka Jörg 
Published: November 2019

AbstractThe Cloud offers enhanced flexibility in the management of resources for any kind of application while it promises the reduction of its cost as well as its infinite scalability. In this way, due to these advantages, there is a recent move towards migrating business processes (BPs) in the Cloud. Such a move is currently performed in a manual manner and only in the context of one Cloud. However, a multi- & cross-Cloud configuration of a BP can be beneficial as it can allow exploiting the best possible offers from multiple Clouds and enable to avoid the lock-in effect by also having the ability to deploy different instances of the BP in different Clouds close to the locations of BP customers. In this respect, this article presents a novel architecture of an environment which realises the vision of multi-Cloud BP provisioning. This environment involves innovative components which support the cross-level orchestration of cloud services as well as the cross-level monitoring and adaptation of BPs. It also relies on a certain language called CAMEL which has been extended to support the adaptive provisioning of multi-Cloud BPs.
Sort of a nice distance: a qualitative study of the experiences of therapists working with internet-based treatment of problematic substance use
Authors: Ekström Veronica , Johansson Magnus 
Published: November 2019

Abstract
Background
Internet interventions have been developed and tested for several psychiatric and somatic conditions. Few people with substance use disorders receive treatment and many drug users say that they would prefer getting help from online tools. Internet interventions are effective for reducing alcohol and cannabis use. The aim of the current study is to understand differences between internet-based and face-to-face treatment of problematic substance use. The concept of alliance will be used as a theoretical frame for understanding differences between internet-based treatment and face-to-face treatment, as perceived by therapists.

Method
The study has a qualitative design and is based on 3 focus group interviews with 12 therapists working with internet-based treatment for alcohol or cannabis use problems within five different programs.

Results
The analysis revealed five themes in the differences between internet-based and face-to-face treatment: communication, anonymity, time, presence and focus. Treatment online in written and asynchronous form creates something qualitatively different from regular face-to-face meetings between patients and therapists. The written form changes the concept of time in treatment, that is, how time can be used and how it affects the therapist’s presence. The asynchronous (i.e. time delayed) form of communication and the lack of facial expressions and body language require special skills.

Conclusions
There are important differences between internet-based treatment and face-to-face treatment. Different aspects of the alliance seem to be important in internet-based treatment compared to face-to-face.