bluuebunny/crossref_metadata_2025_split huggingface dataset:
‘Where and how do you buy medicines?’ A pilot survey of consumption strategies among the public in Sweden
Authors: Lundin S , Liu R 
Published: June 2019

Abstract

Background
Substandard and falsified (SF) medical products are a major danger to public health. They affect every region of the world, and have been identified in all major therapeutic categories. Studies from medicine, pharmacology, law and public health dominate this research area with a focus on the supply side. However, the spread of SF medical products cannot be fully understood without information about the demand side or a sociocultural perspective on market formation. The aim of this short report is to present findings from a pilot study that examines the attitudes of the Swedish public regarding consumption of medicines.

Methods
We conducted a pilot survey in 2016 ‘Where and how do you buy medicines?’ using LimeSurvey, an open-source online survey software. In total 155 respondents completed the survey.

Results
The majority of respondents turn to doctors within healthcare for prescription-only medicines (POM). Simultaneously, some respondents would consider buying POMs without prior contact with experts even if medicines may come from unsafe sources.

Conclusions
There is a tendency that people move away from formal healthcare towards an unregulated market. In parallel, people’s approach to doctors becomes more personalized and pragmatic than in former patriarchal relationships. Risk becomes a negotiable concept.
Relationships between digestible energy and metabolizable energy in current feedlot diets1
Authors: Hales Kristin E 
Published: June 2019

Abstract
It is commonplace that metabolizable energy (ME) is calculated from digestible energy (DE) as DE × 0.82. However, recent published literature suggests that the relationship between DE and ME is variable depending on the type of diet used, and is typically &gt; 0.90 when high-concentrate diets are fed. Literature means were compiled from 23 respiration calorimetry studies where total fecal and urine collections were conducted and gaseous energy was measured. The relationship between experimentally observed and predicted ME (DE × 0.82) was evaluated using these previously reported treatment means. Additionally, a previously published linear regression equation for predicting ME from DE was also evaluated using a residual analysis. Published (Hales, K. E., A. P. Foote, T. M. Brown-Brandl, and H. C. Freetly. 2017. The effects of feeding increasing concentrations of corn oil on energy metabolism and nutrient balance in finishing beef steers. J. Anim. Sci. 95:939–948. doi:10.2527/jas.2016.0902 and Hemphill, C. N., T. A. Wickersham, J. E. Sawyer, T. M. Brown-Brandl, H. C. Freetly, and K. E. Hales. 2018. Effects of feeding monensin to bred heifers fed in a drylot on nutrient and energy balance. J. Anim. Sci. 96:1171–1180. doi:10.1093/jas/skx030) and unpublished data (K. E. Hales, unpublished data) were used to develop a new equation for estimating ME from DE (megacalories/kilogram [Mcal/kg] of DM; ME = −0.057 ± 0.022 DE2 + 1.3764 ± 0.1197 DE – 0.9483 ± 0.1605; r2 = 0.9671, root mean square error = 0.12; P &lt; 0.01 for intercept, P &lt; 0.01 for linear term, and P &lt; 0.01 for quadratic term). To establish a maximum biological threshold for the conversion of DE to ME, individual animal data were used (n = 234) to regress the ME:DE on DE concentration (1.53 to 3.79 Mcal DE/kg). When using experimentally derived data and solving for the first derivative, the maximum biological threshold for the conversion of DE to ME was 3.65 Mcal DE/kg. Additionally, the quadratic regression (equation 1) was used to predict ME from a wide range of DE (1.8 to 4.6 Mcal/kg). The ME:DE ratio was then calculated by dividing predicted ME by DE. The maximum biological threshold for the conversion of DE to ME was estimated by solving for the first derivative and was 3.96 Mcal DE/kg. In conclusion, this review suggests that the relationship between DE and ME is not static, especially in high-concentrate diets. The equation presented here is an alternative that can be used for the calculation of ME from DE in current feedlot diets, but it is not recommended for use in high-forage diets. The maximization of ME in current diets, maximum biological threshold, occurs between 3.65 and 3.96 Mcal DE/kg in the diet, which based on these data is approximately 3.43 to 3.65 Mcal/kg of ME consumption.
Individualization of Migraine Prevention
Authors: Kisler Lee B. , Weissman-Fogel Irit , Coghill Robert C. , Sprecher Elliot , Yarnitsky David , Granovsky Yelena 
Published: June 2019

Objective:Finding an effective preventive agent for the individual migraineur is often long and frustrating. An individual-specific, efficacy-predicting tool would be invaluable in directing, shortening, and improving this process. As the serotonin-norepinephrine reuptake inhibitor duloxetine is a pain modulator, we hypothesized that pronociceptivity will directly predict drug efficacy, so that the more pronociceptive the patient is, the more efficacious the drug. Therefore, we used psychophysical pain measures to predict duloxetine efficacy in migraine prevention.Methods:Fifty-five migraineurs participated: 27 received duloxetine and 28 nonactive placebo. Responses to painful stimuli, conditioned pain modulation, and temporal summation of pain were measured before treatment. Treatment outcome measures included changes in attack frequency, migraine days, pain levels, and a reported self-estimate of migraine improvement at weeks 4 and 5. To examine treatment effects, the outcome measures were compared with pretreatment levels. Treatment by the psychophysical-predictor effect on treatment outcome was examined in separate regression models.Results:Duloxetine was more efficacious than placebo in migraine prevention, as indicated by the patient’s estimation of migraine improvement (duloxetine: 52.3±30.4%; placebo: 26.0±27.3%;P=0.001). Further, this measure, in the duloxetine group, was predicted by higher pretreatment pain ratings for tonic heat pain (P=0.012); greater pain sensitivity at baseline predicted greater percent of migraine improvement in duloxetine (r=0.47;P=0.013), but not in placebo (r=−0.36;P=0.060).Discussion:Our results suggest how personalized medicine can be applied to designing appropriate migraine prevention treatment. Psychophysical testing can reveal and characterize pronociceptive migraineurs, who seem to be more likely than non–pronociceptive ones to benefit from migraine prevention with serotonin-norepinephrine reuptake inhibitors.
The Efficacy of Outpatient Pulmonary Rehabilitation After Bilateral Lung Transplantation
Authors: Candemir Ipek , Ergun Pinar , Kaymaz Dicle , Demir Neşe , Taşdemir Filiz , Sengul Fatma , Egesel Nurcan , Yekeler Erdal 
Published: June 2019

Purpose:
Pulmonary rehabilitation (PR) is advocated in the pre- and post–lung transplantation (LTx) periods. However, there is limited literature on the benefit of PR post-LTx. The aim of this study was to investigate the efficacy of an outpatient, multidisciplinary, comprehensive PR program in bilateral LTx recipients in the early period after LTx.

Method:
Twenty-three LTx recipients were referred to the PR center. Change in incremental and endurance shuttle walk tests, hand and quadriceps strength, respiratory muscle strength (maximum inspiratory/expiratory pressure), dyspnea (Medical Research Council score), quality of life (St George's Respiratory Questionnaire, Chronic Respiratory Questionnaire), and psychological status (Hospital Anxiety Depression Scale) were compared pre- and post-PR.

Results:
Seventeen of 23 (74%) recipients completed PR, comprising 15 male and 2 female patients whose median age was 51 yr. The initiation of the program was 75 ± 15 d after LTx. The incremental shuttle walk test distance was predicted as 23% before PR and it increased to 36% after PR (P < .001); the endurance shuttle walk test distance also increased (P < .01). Significant improvement was seen in upper and lower extremity strength, and St George's Respiratory Questionnaire and Chronic Respiratory Questionnaire scores and Hospital Anxiety Depression Scale scores reflected less anxiety and depressive symptoms. Furthermore, body mass and fat-free mass indices, maximum inspiratory pressure, and maximum expiratory pressure improved significantly. There was no significant change in forced expiratory volume in the first second of expiration, forced vital capacity, or Medical Research Council scores.

Conclusion:
This study demonstrated that patients who attended PR within 3 mo of bilateral LTx showed improvements in exercise capacity, respiratory muscle strength, quality of life, body composition, and psychological status.
Topical Nifedipine for the Treatment of Pressure Ulcer: A Randomized, Placebo-Controlled Clinical Trial
Authors: Zolfagharnezhad Hedieh , Khalili Hossein , Mohammadi Mostafa , Niknam Somayeh , Vatanara Alireza 
Published: June 2019

Background:
Effect of nifedipine on pressure ulcer (PU) healing has not been evaluated in the human subjects yet.

Study question:
In this study, the effect of topical application of nifedipine 3% ointment on PU healing in critically ill patients was investigated.

Study design:
This was a randomized, double-blind, placebo-controlled clinical.

Measures and outcomes:
In this study, 200 patients with stage I or II PU according to 2-digit Stirling Pressure Ulcer Severity Scale were randomized to receive topical nifedipine 3% ointment or placebo twice daily for 14 days. Changes in the size and stage of the ulcers were considered as primary outcome of the study. The stage of the ulcers at baseline and on day 7 and day 14 of study was determined by using 2-digit stirling scale. In addition, the surface area of the wounds was estimated by multiplying width by length.

Results:
In total, 83 patients in each group completed the study. The groups were matched for the baseline stage and size of PUs. Mean decrease in the stage of PU in the nifedipine group was significantly higher than the placebo group on day 7 (−1.71 vs. −0.16, respectively, P < 0.001) and day 14 (−0.78 vs. −0.09, respectively, P < 0.001). Furthermore, the mean decrease in the surface area of PU was significantly higher in the nifedipine group compared with the placebo group on day 7 (−1.44 vs. −0.32, respectively, P < 0.001) and day 14 (−2.51 vs. −0.24, respectively, P < 0.001) of study.

Conclusions:
Topical application of nifedipine 3% ointment for 14 days significantly improved the healing process of stage I or II PUs in critically ill patients.
Bioaccumulation of heavy metals in commercially important fish species from the tropical river estuary suggests higher potential child health risk than adults
Authors: Ahmed A. S. Shafiuddin , Sultana Sharmin , Habib Ahasan , Ullah Hadayet , Musa Najiah , Rahman Md. Mahfujur , Sarker Md. Shafiqul Islam 
Published: June 2019

AbstractThe Karnaphuli, a major river of Bangladesh, located off the coast of Chittagong in the Bay of Bengal is largely exposed to the heavy metal pollutants, which may be toxic to humans and aquatic fauna. The estuary is a striking example of a site where human pressure and ecological values collide with each other. In spite of being a major supplier of fish food for local community, there has been no study carried out to date to assess the potential human health risk due to heavy metal contamination in the fish species from this estuary. Therefore, the aim of present study was to assess bioaccumulation status and the potential human health risk evaluation for local consumers. Six commercially important fish species, Apocryptes bato, Pampus chinensis, Hyporhamphus limbatus, Liza parsia, Mugil cephalus, and Tenualosa toil from the Karnaphuli River estuary were collected to analyze heavy metals concentration level. Heavy metals As, Pb, Cd, Cr and Cu were detected from the samples using inductively coupled plasma mass spectrometry (Model: ELAN9000, Perkin-Elmer, Germany). The hierarchy of the measured concentration level of the metals was as follows: Pb (mean: 13.88, range: 3.19 - 6.19) > Cu (mean: 12.10, range: 10.27 - 16.41) > As (mean: 4.89, range: 3.19 – 6.19) > Cr (mean: 3.36, range: 2.46 – 4.17) > Cd (mean: 0.39, range: 0.21 - 0.74). The Fulton’s condition factor denoted that organisms were particularly in better ‘condition’ and most of the species were in positive allometric growth. The Bioaccumulation factors (BAFs) observed in the species of the contaminants were organized in the following ranks: Cu (1971.42) > As (1042.93) > Pb (913.66) > Cr (864.99) > Cd (252.03), and among all the specimens, demersal fish, A. bato corresponded to the maximum bio-accumulative organism. Estimated daily intake (EDI), target hazard quotient (THQ) and carcinogenic risk (CR) assessed for human health risk implications suggest that the values are within the acceptable threshold for all sorts of consumers. Hence none of them would experience non-carcinogenic and carcinogenic health effect for the ingestion of the fishes. However, children are shown to be largely susceptible than adults to non-carcinogenic and carcinogenic health effect due to the consumption of fish. Therefore, an appropriate guidlines and robust management measures needed to be taken to restore the estuarine health condition for greater benefit of the quality of fish products for local consumption.Graphical abstract
Graph analytics for phenome-genome associations inference
Authors: Cirillo Davide , Garcia-Gasulla Dario , Cortés Ulises , Valencia Alfonso 
Published: June 2019

AbstractMotivationBiological ontologies, such as the Human Phenotype Ontology (HPO) and the Gene Ontology (GO), are extensively used in biomedical research to find enrichment in the annotations of specific gene sets. However, the interpretation of the encoded information would greatly benefit from methods that effectively interoperate between multiple ontologies providing molecular details of disease-related features.ResultsIn this work, we present a statistical framework based on graph theory to infer direct associations between HPO and GO terms that do not share co-annotated genes. The method enables to map genotypic features to phenotypic features thus providing a valid tool for bridging functional and pathological annotations. We validated the results by (a) supporting evidence of known drug-target associations (PanDrugs), protein-protein physical and functional interactions (BioGRID and STRING), and common pathways (Reactome); (b) comparing relationships inferred from early ontology releases with knowledge contained in the latest versions.ApplicationsWe applied our method to improve the interpretation of molecular processes involved in pathological conditions, illustrating the applicability of our predictions with a number of biological examples. In particular, we applied our method to expand the list of relevant genes from standard functional enrichment analysis of high-throughput experimental results in the context of comorbidities between Alzheimer’s disease, Lung Cancer and Glioblastoma. Moreover, we analyzed pathways linked to predicted phenotype-genotype associations getting insights into the molecular actors of cellular senescence in Proteus syndrome.Availabilityhttps://github.com/dariogarcia/phenotype-genotype_graph_characterization
Nitric oxide acts as a cotransmitter in a subset of dopaminergic neurons to diversify memory dynamics
Authors: Aso Yoshinori , Ray Robert , Long Xi , Cichewicz Karol , Ngo Teri-TB , Sharp Brandi , Christoforou Christina , Lemire Andrew , Hirsh Jay , Litwin-Kumar Ashok , Rubin Gerald M. 
Published: June 2019

SummaryAnimals employ multiple and distributed neuronal networks with diverse learning rules and synaptic plasticity dynamics to record distinct temporal and statistical information about the world. However, the molecular mechanisms underlying this diversity are poorly understood. The anatomically defined compartments of the insect mushroom body function as parallel units of associative learning, with different learning rates, memory decay dynamics and flexibility (Aso & Rubin 2016). Here we show that nitric oxide (NO) acts as a neurotransmitter in a subset of dopaminergic neurons in Drosophila. NO’s effects develop more slowly than those of dopamine and depend on soluble guanylate cyclase in postsynaptic Kenyon cells. NO acts antagonistically to dopamine; it shortens memory retention and facilitates the rapid updating of memories. The interplay of NO and dopamine enables memories stored in local domains along Kenyon cell axons to be specialized for predicting the value of odors based only on recent events. Our results provide key mechanistic insights into how diverse memory dynamics are established in parallel memory systems.
Regulation of terminal hypertrophic chondrocyte differentiation inPrmt5mutant mice modeling infantile idiopathic scoliosis
Authors: Liu Zhaoyang , Ramachandran Janani , Vokes Steven A , Gray Ryan S 
Published: June 2019

ABSTRACTIdiopathic scoliosis (IS) is the most common type of musculoskeletal defect effecting children and is classified by age of onset, location, and degree of spine curvature. Although rare, the onset of IS during infancy is the more severe and rapidly progressive form of the disease, leading to increased mortality due to significant respiratory compromise. The pathophysiology of IS, in particular for infantile IS, remain elusive. Here, we show that PRMT5 is critical for the regulation of terminal hypertrophic chondrocyte differentiation in the spine and models infantile IS in mouse. Conditional ablation of PRMT5 in osteochondral progenitors led to impaired terminal hypertrophic chondrocyte differentiation and asymmetric defects of endochondral bone formation in the perinatal spine. Analysis of several markers of endochondral ossification revealed increased COLX andIhhexpression and a dramatic reduction ofMmp13and RUNX2 expression in the intervertebral disc and vertebral growth plate. Furthermore, we demonstrate that PRMT5 function in committed chondrogenic lineages is required for regulation of COLX expression in the adult spine. Together, our results establish PRMT5 as a critical regulator of hypertrophic chondrocyte differentiation and endochondral bone formation in spine development and maintenance.
Long non-coding RNA expression levels modulate cell-type specific splicing patterns by altering their interaction landscape with RNA-binding proteins
Authors: Porto Felipe Wendt , Daulatabad Swapna Vidhur , Janga Sarath Chandra 
Published: June 2019

AbstractBackgroundRecent developments in our understanding of the interactions between long non-coding RNAs (lncRNAs) and cellular components have improved treatment approaches for various human diseases including cancer, vascular diseases, and neurological diseases. Although investigation of specific lncRNAs revealed their role in the metabolism of cellular RNA, our understanding of their contribution to post-transcriptional regulation is relatively limited. In this study, we explore the role of lncRNAs in modulating alternative splicing and their impact on downstream protein-RNA interaction networks.ResultsAnalysis of alternative splicing events across 39 lncRNA knockdown and wildtype RNA-sequencing datasets from three human cell lines: HeLa (Cervical Cancer), K562 (Myeloid Leukemia), and U87 (Glioblastoma), resulted in high confidence (fdr < 0.01) identification of 11630 skipped exon events and 5895 retained intron events, implicating 759 genes to be impacted at post-transcriptional level due to the loss of lncRNAs. We observed that a majority of the alternatively spliced genes in a lncRNA knockdown were specific to the cell type, in tandem, the functions annotated to the genes affected by alternative splicing across each lncRNA knockdown also displayed cell type specificity. To understand the mechanism behind this cell-type specific alternative splicing patterns, we analyzed RNA binding protein (RBP)-RNA interaction profiles across the spliced regions, to observe cell type specific alternative splice event RBP binding preference.ConclusionsDespite limited RBP binding data across cell lines, alternatively spliced events detected in lncRNA perturbation experiments were associated with RBPs binding in proximal intron-exon junctions, in a cell type specific manner. The cellular functions affected by alternative splicing were also affected in a cell type specific manner. Based on the RBP binding profiles in HeLa and K562 cells, we hypothesize that several lncRNAs are likely to exhibit a sponge effect in disease contexts, resulting in the functional disruption of RBPs, and their downstream functions. We propose that such lncRNA sponges can extensively rewire the post-transcriptional gene regulatory networks by altering the protein-RNA interaction landscape in a cell-type specific manner.
Modeling and performance analysis of machining fixture for near-net-shaped jet engine blade
Authors: Wang Hui , Peng Jingsong , Zhao Bing , Zhang Xin-Dong , Yu Jie , Li Yuan , Wang Mao-Min 
Published: June 2019

PurposeNear-net-shaped processes of jet engine blade have better performance in both reducing the material waste during production and improving work reliability in service, while the geometric features of blade, both sculptured surface and thin-walled shape, make the precise machining of blade challenging and difficult owing to its dynamics behaviors under complex clamping and machining loads. This paper aims to present a fundamental approach on modeling and performance analysis of the blade–fixture system.Design/methodology/approachA computerized framework on the complex blade–fixture dynamic behavior has been developed. Theoretical mechanic analysis on blade fixturing and machining is proposed with an especial emphasis on the boundary conditions of the blade–fixture system. Then the finite element analysis (FEA) method is used to simulate the variation trend of preloads, stiffness and blade distortion. The strong influence of parameters of workpiece–fixture configuration on blade distortion and machining error is investigated.FindingsWith a case of real jet engine blade machining, the experimental results and theoretical predictions suggest good agreement on their variation tendency. The loaded pressure of clamps has a critical influence on the total stiff performance of the blade–fixture system, and the profile error of the blade contributes much to the inconsistency in geometric dimension and surface integrity of blades’ machining. In the end, the results also validate the effectiveness of this methodology to predict and improve the performance of the blade–fixture configuration design.Originality/valueThe adaptive machining of near-net-shaped jet engine blade is a new high-performance manufacturing technology in aerospace production. This study provides a fundamental methodology for the performance analysis of blade-fixture system, to clear the variation law of blade distortion during preloading and machining, which will contribute to minimize the machining error and improve productivity.