bluuebunny/crossref_metadata_2025_split huggingface dataset:
REVEALING AND ACKNOWLEDGING VALUE JUDGMENTS IN HEALTH TECHNOLOGY ASSESSMENT
Authors: Hofmann Bjørn , Cleemput Irina , Bond Kenneth , Krones Tanja , Droste Sigrid , Sacchini Dario , Oortwijn Wija 
Published: March 2015

Background:Although value issues are increasingly addressed in health technology assessment (HTA) reports, HTA is still seen as a scientific endeavor and sometimes contrasted with value judgments, which are considered arbitrary and unscientific. This article aims at illustrating how numerous value judgments are at play in the HTA process, and why it is important to acknowledge and address value judgments.Methods:A panel of experts involved in HTA, including ethicists, scrutinized the HTA process with regard to implicit value judgments. It was analyzed whether these value judgments undermine the accountability of HTA results. The final results were obtained after several rounds of deliberation.Results:Value judgments are identified before the assessment when identifying and selecting health technologies to assess, and as part of assessment. They are at play in the processes of deciding on how to select, frame, present, summarize or synthesize information in systematic reviews. Also, in economic analysis, value judgments are ubiquitous. Addressing the ethical, legal, and social issues of a given health technology involves moral, legal, and social value judgments by definition. So do the appraisal and the decision-making process.Conclusions:HTA by and large is a process of value judgments. However, the preponderance of value judgments does not render HTA biased or flawed. On the contrary they are basic elements of the HTA process. Acknowledging and explicitly addressing value judgments may improve the accountability of HTA.
EARLY DIALOGUE WITH HEALTH TECHNOLOGY ASSESSMENT BODIES: A EUROPEAN PERSPECTIVE
Authors: Cuche Matthieu , Beckerman Rachel , Chowdhury Cyrus A. , van Weelden Marije A. 
Published: March 2015

Introduction: Evidence requirements may differ across HTA bodies, and so pharmaceutical companies must plan to synergize their evidence generation strategy, across global regulatory and HTA bodies. Until recently, companies had no official platform to discuss the clinical development of a drug with HTA bodies; however, this is changing.Objectives: To achieve broad usage in the EU, products must achieve both regulatory and reimbursement approval, the latter of which is based on HTA appraisal in many markets. The objective of this study is to present and evaluate the different options available for early HTA consultation (during drug development/Phase III) in the major European markets from the industry perspective.Methods: An exploratory (nonsystematic) literature review was performed to identify the European markets offering early HTA consultations, and each process was analyzed using a set of predefined metrics that are relevant to industry (the ability to consult with the regulatory body in parallel, consultation fees, length of consultation meeting, language of consultation meeting, maximum number of pharmaceutical company employees attending, procedural timelines, nature of data for which consultative advice can be sought, the output of the process, and the ability to involve external experts).Results: Four different types of early HTA consultation processes were identified across the major European HTA markets. The nature of these processes varied in terms of the types and number of questions that can be addressed, the length of the meeting, the reporting output, and the ability to involve external experts.Conclusions: The availability of various options for early HTA consultation may help to avoid a mismatch between the evidence generated by means of a product's clinical development program, and the evidence expected by HTA bodies and payers, which can facilitate the pricing and reimbursement process upon a product's market authorization.
BELGIAN GUIDELINES FOR ECONOMIC EVALUATIONS: SECOND EDITION
Authors: Thiry Nancy , Neyt Mattias , Van De Sande Stefaan , Cleemput Irina 
Published: March 2015

Objectives:The aim of this study was to present the updated methodological guidelines for economic evaluations of healthcare interventions (drugs, medical devices, and other interventions) in Belgium.Methods:The update of the guidelines was performed by three Belgian health economists following feedback from users of the former guidelines and personal experience. The updated guidelines were discussed with a multidisciplinary team consisting of other health economists, assessors of reimbursement request files, representatives of Belgian databases and representatives of the drugs and medical devices industry. The final document was validated by three external validators that were not involved in the previous discussions.Results:The guidelines give methodological guidance for the following components of an economic evaluation: literature review, perspective of the evaluation, definition of the target population, choice of the comparator, analytic technique and study design, calculation of costs, valuation of outcomes, definition of the time horizon, modeling, handling uncertainty and discounting. We present a reference case that can be considered as the minimal requirement for Belgian economic evaluations of health interventions.Conclusions:These guidelines will improve the methodological quality, transparency and uniformity of the economic evaluations performed in Belgium. The guidelines will also provide support to the researchers and assessors performing or evaluating economic evaluations.
Rasch Modeling and Confirmatory Factor Analysis of the Systemizing Quotient-Revised (SQ-R) Scale
Authors: Allison Carrie , Baron-Cohen Simon , Stone Mark H , Muncer Steven J 
Published: March 2015

AbstractThis study assessed the dimensionality of the Systemizing Quotient-Revised (SQ-R), a measure of how strong a person's interest is in systems, using two statistical approaches: Rasch modeling and Confirmatory Factor Analysis (CFA). Participants included N = 675 with an autism spectrum condition (ASC), N = 1369 family members of people with ASC, and N = 2014 typical controls. Data were applied to the Rasch model (Rating Scale) using WINSTEPS. The data fit the Rasch model quite well lending support to the idea that systemizing could be seen as unidimensional. Reliability estimates were .99 for items and .92 for persons. A CFA parceling approach confirmed that a unidimensional model fit the data. There was, however, differential functioning by sex in some of these items. An abbreviated 44-item version of the scale, consisting of items without differential item functioning by sex was developed. This shorter scale also was tested from a Rasch perspective and confirmed through CFA. All measures showed differences on total scale scores between those participants with and without ASC (d = 0.71, p < .005), and between sexes (d = 0.53, p < .005). We conclude that the SQ-R is an appropriate measure of systemizing which can be measured along a single dimension.
Strain-induced metal–semiconductor transition observed in atomic carbon chains
Authors: La Torre A. , Botello-Mendez A. , Baaziz W. , Charlier J. -C. , Banhart F. 
Published: March 2015

AbstractCarbyne, the sp1-hybridized phase of carbon, is still a missing link in the family of carbon allotropes. While the bulk phases of carbyne remain elusive, the elementary constituents, that is, linear chains of carbon atoms, have already been observed using the electron microscope. Isolated atomic chains are highly interesting one-dimensional conductors that have stimulated considerable theoretical work. Experimental information, however, is still very limited. Here we show electrical measurements and first-principles transport calculations on monoatomic carbon chains. When the 1D system is under strain, the chains are semiconducting corresponding to the polyyne structure with alternating bond lengths. Conversely, when the chain is unstrained, the ohmic behaviour of metallic cumulene with uniform bond lengths is observed. This confirms the recent prediction of a metal–insulator transition that is induced by strain. The key role of the contacting leads explains the rectifying behaviour measured in monoatomic carbon chains in a nonsymmetric contact configuration.
Conservation of writhe helicity under anti-parallel reconnection
Authors: Laing Christian E. , Ricca Renzo L. , Sumners De Witt L. 
Published: March 2015

AbstractReconnection is a fundamental event in many areas of science, from the interaction of vortices in classical and quantum fluids and magnetic flux tubes in magnetohydrodynamics and plasma physics, to the recombination in polymer physics and DNA biology. By using fundamental results in topological fluid mechanics, the helicity of a flux tube can be calculated in terms of writhe and twist contributions. Here we show that the writhe is conserved under anti-parallel reconnection. Hence, for a pair of interacting flux tubes of equal flux, if the twist of the reconnected tube is the sum of the original twists of the interacting tubes, then helicity is conserved during reconnection. Thus, any deviation from helicity conservation is entirely due to the intrinsic twist inserted or deleted locally at the reconnection site. This result has important implications for helicity and energy considerations in various physical contexts.
Identification of proteins responsible for adriamycin resistance in breast cancer cells using proteomics analysis
Authors: Wang Zhipeng , Liang Shuang , Lian Xin , Liu Lei , Zhao Shu , Xuan Qijia , Guo Li , Liu Hang , Yang Yuguang , Dong Tieying , Liu Yanchen , Liu Zhaoliang , Zhang Qingyuan 
Published: March 2015

AbstractChemoresistance is a poor prognostic factor in breast cancer and is a major obstacle to the successful treatment of patients receiving chemotherapy. However, the precise mechanism of resistance remains unclear. In this study, a pair of breast cancer cell lines, MCF-7 and its adriamycin-resistant counterpart MCF-7/ADR was used to examine resistance-dependent cellular responses and to identify potential therapeutic targets. We applied nanoflow liquid chromatography (nLC) and tandem mass tags (TmT) quantitative mass spectrometry to distinguish the differentially expressed proteins (DEPs) between the two cell lines. Bioinformatics analyses were used to identify functionally active proteins and networks. 80 DEPs were identified with either up- or down-regulation. Basing on the human protein-protein interactions (PPI), we have retrieved the associated functional interaction networks for the DEPs and analyzed the biological functions. Six different signaling pathways and most of the DEPs strongly linked to chemoresistance, invasion, metastasis development, proliferation and apoptosis. The identified proteins in biological networks served to resistant drug and to select critical candidates for validation analyses by western blot. The glucose-6-phosphate dehydrogenase (G6PD), gamma-glutamyl cyclotransferase (GGCT), isocitrate dehydrogenase 1 (NADP+,soluble)(IDH1), isocitrate dehydrogenase 2 (NADP+,mitochondrial) (IDH2) and glutathione S-transferase pi 1(GSTP1), five of the critical components of GSH pathway, contribute to chemoresistance.
Lactobacillus rhamnosus lowers zebrafish lipid content by changing gut microbiota and host transcription of genes involved in lipid metabolism
Authors: Falcinelli Silvia , Picchietti Simona , Rodiles Ana , Cossignani Lina , Merrifield Daniel L. , Taddei Anna Rita , Maradonna Francesca , Olivotto Ike , Gioacchini Giorgia , Carnevali Oliana 
Published: March 2015

AbstractThe microbiome plays an important role in lipid metabolism but how the introduction of probiotic communities affects host lipid metabolism is poorly understood. Using a multidisciplinary approach we addressed this knowledge gap using the zebrafish model by coupling high-throughput sequencing with biochemical, molecular and morphological analysis to evaluate the changes in the intestine. Analysis of bacterial 16S libraries revealed thatLactobacillus rhamnosuswas able to modulate the gut microbiome of zebrafish larvae, elevating the abundance of Firmicutes sequences and reducing the abundance of Actinobacteria. The gut microbiome changes modulated host lipid processing by inducing transcriptional down-regulation of genes involved in cholesterol and triglycerides metabolism (fit2, agpat4, dgat2, mgll,hnf4α, scapandcck) concomitantly decreasing total body cholesterol and triglyceride content and increasing fatty acid levels.L. rhamnosustreatment also increased microvilli and enterocyte lengths and decreased lipid droplet size in the intestinal epithelium. These changes resulted in elevated zebrafish larval growth. This integrated system investigation demonstrates probiotic modulation of the gut microbiome, highlights a novel gene network involved in lipid metabolism, provides an insight into how the microbiome regulates molecules involved in lipid metabolism and reveals a new potential role forL. rhamnosusin the treatment of lipid disorders.
Phylogenomic analysis uncovers the evolutionary history of nutrition and infection mode in rice blast fungus and other Magnaporthales
Authors: Luo Jing , Qiu Huan , Cai Guohong , Wagner Nicole E. , Bhattacharya Debashish , Zhang Ning 
Published: March 2015

AbstractThe order Magnaporthales (Ascomycota, Fungi) includes devastating pathogens of cereals, such as the rice blast fungus Pyricularia (Magnaporthe) oryzae, which is a model in host-pathogen interaction studies. Magnaporthales also includes saprotrophic species associated with grass roots and submerged wood. Despite its scientific and economic importance, the phylogenetic position of Magnaporthales within Sordariomycetes and the interrelationships of its constituent taxa, remain controversial. In this study, we generated novel transcriptome data from 21 taxa that represent key Magnaporthales lineages of different infection and nutrition modes and phenotypes. Phylogenomic analysis of >200 conserved genes allowed the reconstruction of a robust Sordariomycetes tree of life that placed the monophyletic group of Magnaporthales sister to Ophiostomatales. Among Magnaporthales, three major clades were recognized: 1) an early diverging clade A comprised of saprotrophs associated with submerged woods; 2) clade B that includes the rice blast fungus and other pathogens that cause blast diseases of monocot plants. These species infect the above-ground tissues of host plants using the penetration structure, appressorium; and 3) clade C comprised primarily of root-associated species that penetrate the root tissue with hyphopodia. The well-supported phylogenies provide a robust framework for elucidating evolution of pathogenesis, nutrition modes and phenotypic characters in Magnaporthales.
Association of Body Mass Index with Chromosome Damage Levels and Lung Cancer Risk among Males
Authors: Li Xiaoliang , Bai Yansen , Wang Suhan , Nyamathira Samuel Mwangi , Zhang Xiao , Zhang Wangzhen , Wang Tian , Deng Qifei , He Meian , Zhang Xiaomin , Wu Tangchun , Guo Huan 
Published: March 2015

AbstractEpidemiological studies have shown an etiological link between body mass index (BMI) and cancer risk, but evidence supporting these observations is limited. This study aimed to investigate potential associations of BMI with chromosome damage levels and lung cancer risk. First, we recruited 1333 male workers from a coke-oven plant to examine their chromosome damage levels; and then, a cohort study of 12 052 males was used to investigate the association of BMI with lung cancer incidence. We further carried out a meta-analysis for BMI and male lung cancer risk based on cohort studies. We found that men workers with excess body weight (BMI ≥ 25 kg/m2) had lower levels of MN frequencies than men with normal-weight (BMI: 18.5–24.9). Our cohort study indicated that, the relative risk (RR) for men with BMI ≥ 25 to develop lung cancer was 35% lower than RR for normal-weight men. Further meta-analysis showed that, compared to normal-weight men, men with BMI ≥ 25 had decreased risk of lung cancer among both the East-Asians and others populations. These results indicate that men with excess body weight had significant decreased chromosome damage levels and lower risk of lung cancer than those with normal-weight. However, further biological researches were needed to validate these associations.
Metastability in lipid based particles exhibits temporally deterministic and controllable behavior
Authors: Jacoby Guy , Cohen Keren , Barkan Kobi , Talmon Yeshayahu , Peer Dan , Beck Roy 
Published: March 2015

AbstractThe metastable-to-stable phase-transition is commonly observed in many fields of science, as an uncontrolled independent process, highly sensitive to microscopic fluctuations. In particular, self-assembled lipid suspensions exhibit phase-transitions, where the underlying driving mechanisms and dynamics are not well understood. Here we describe a study of the phase-transition dynamics of lipid-based particles, consisting of mixtures of dilauroylphosphatidylethanolamine (DLPE) and dilauroylphosphatidylglycerol (DLPG), exhibiting a metastable liquid crystalline-to-stable crystalline phase transition upon cooling from 60°C to 37°C. Surprisingly, unlike classically described metastable-to-stable phase transitions, the manner in which recrystallization is delayed by tens of hours is robust, predetermined and controllable. Our results show that the delay time can be manipulated by changing lipid stoichiometry, changing solvent salinity, adding an ionophore, or performing consecutive phase-transitions. Moreover, the delay time distribution indicates a deterministic nature. We suggest that the non-stochastic physical mechanism responsible for the delayed recrystallization involves several rate-affecting processes, resulting in a controllable, non-independent metastability. A qualitative model is proposed to describe the structural reorganization during the phase transition.
The importance of sensory integration processes for action cascading
Authors: Gohil Krutika , Stock Ann-Kathrin , Beste Christian 
Published: March 2015

AbstractDual tasking or action cascading is essential in everyday life and often investigated using tasks presenting stimuli in different sensory modalities. Findings obtained with multimodal tasks are often broadly generalized, but until today, it has remained unclear whether multimodal integration affects performance in action cascading or the underlying neurophysiology. To bridge this gap, we asked healthy young adults to complete a stop-change paradigm which presented different stimuli in either one or two modalities while recording behavioral and neurophysiological data. Bimodal stimulus presentation prolonged response times and affected bottom-up and top-down guided attentional processes as reflected by the P1 and N1, respectively. However, the most important effect was the modulation of response selection processes reflected by the P3 suggesting that a potentially different way of forming task goals operates during action cascading in bimodal vs. unimodal tasks. When two modalities are involved, separate task goals need to be formed while a conjoint task goal may be generated when all stimuli are presented in the same modality. On a systems level, these processes seem to be related to the modulation of activity in fronto-polar regions (BA10) as well as Broca's area (BA44).
Spatial training preserves associative memory capacity with augmentation of dendrite ramification and spine generation in Tg2576 mice
Authors: Jiang Xia , Chai Gao-Shang , Wang Zhi-Hao , Hu Yu , Li Xiao-Guang , Ma Zhi-Wei , Wang Qun , Wang Jian-Zhi , Liu Gong-Ping 
Published: March 2015

AbstractAlzheimer's disease (AD) is the most common neurodegenerative disorder and there is currently no efficient cure for this devastating disease. Cognitive stimulation can delay memory loss during aging and in patients with mild cognitive impairment. In 3 × Tg-AD mice, training decreased the neuropathologies with transient amelioration of memory decline. However, the neurobiological mechanisms underlying the learning-improved memory capacity are poorly understood. Here, we found in Tg2576 mice spatial training in Morris water maze (MWM) remarkably improved the subsequent associative memory acquisition detected by contextual fear conditioning. We also found that spatial training enhanced long term potentiation, dendrite ramification and spine generation in hippocampal dentate gyrus (DG) and CA1 neurons at 24 h after the training. In the molecular level, the MWM training remarkably activated calcium/calmodulin-dependent protein kinase II (CaMKII) with elevation of glutamate AMPA receptor GluA1 subunit (GluA1), postsynaptic density protein 93 (PSD93) and postsynaptic density protein 95 (PSD95) in the hippocampus. Finally, the training also significantly ameliorated AD-like tau and amyloid pathologies. We conclude that spatial training in MWM preserves associative memory capacity in Tg2576 mice and the mechanisms involve augmentation of dendrite ramification and spine generation in hippocampus.
Novel Role of Mitochondrial Manganese Superoxide Dismutase in STAT3 Dependent Pluripotency of Mouse Embryonic Stem Cells
Authors: Sheshadri Preethi , Ashwini Ashwathnarayan , Jahnavi Sowmya , Bhonde Ramesh , Prasanna Jyothi , Kumar Anujith 
Published: March 2015

AbstractLeukemia Inhibitory Factor (LIF)/Signal transducer and activator of transcription 3 (STAT3) signaling pathway maintains the stemness and pluripotency of mouse embryonic stem cells (mESCs). Detailed knowledge on key intermediates in this pathway as well as any parallel pathways is largely missing. We initiated our study by investigating the effect of small molecule Curcumin on various signalling pathways essential for self-renewal. Curcumin sustained the LIF independent self-renewal of mESCs and induced pluripotent stem cells (miPSCs) in a STAT3 activity dependent manner. Gene expression analysis showed LIF/STAT3 and redox signaling components to be majorly modulated. Amongst ROS genes, expression of Manganese Superoxide Dismutase (MnSOD) specifically relied on STAT3 signaling as evidenced by STAT3 inhibition and reporter assay. The silencing of MnSOD, but not Cu-ZnSOD expression, resulted in the loss of mESC pluripotency in presence of LIF and the overexpression of MnSOD is sufficient for maintaining the expression of pluripotent genes in the absence of STAT3 signaling. Finally, we demonstrate MnSOD to stabilize the turnover of pluripotent proteins at the post-translational level by modulating proteasomal activity. In conclusion, our findings unravel a novel role of STAT3 mediated MnSOD in the self-renewal of mESCs.