bluuebunny/crossref_metadata_2025_split huggingface dataset:
The desire to hasten death: Using Grounded Theory for a better understanding “When perception of time tends to be a slippery slope”
Authors: Pestinger Martina , Stiel Stephanie , Elsner Frank , Widdershoven Guy , Voltz Raymond , Nauck Friedemann , Radbruch Lukas 
Published: March 2015

Background: Some patients with advanced and progressive diseases express a desire to hasten death. Aim: This study evaluated the motivations of patients expressing such a desire in a country with prohibitive legislation on euthanasia and physician-assisted suicide. Design: A modified form of Grounded Theory was used. Setting/participants: Patients from the departments of palliative medicine in three hospitals in Germany were recruited when they had made a statement or request to hasten death. Participants were interviewed face to face. Recruitment was stopped with 12 participants because of data saturation. Results: Thematic analysis revealed three main motivational themes: self-determination, agony, and time. Expectations toward health professionals, attitudes toward death, and secureness related to the end of life were additional main themes emerging from the analysis. Conclusions: The desire to hasten death may be used as an extreme coping strategy to maintain control against anticipated agony. Patients expected health professionals to listen to and respect their experiences. Emerging hypotheses included the following: (a) patients try to balance life time and anticipated agony, and the perception of time is distressing in this balancing act; (b) anticipated images of agony and suffering in the dying process occur frequently and are experienced by patients as intrusive; (c) patients expressing a desire to hasten death are in need of more information about the dying process; and (d) patients wanted their caregivers to listen to and respect their wish to hasten death, and they did not expect the caregivers to understand this as an order to actually hasten their death.
Adherence to highly active antiretroviral therapy in Hyderabad, India: barriers, facilitators and identification of target groups
Authors: Dworkin Mark S , Douglas GW , Rani GP Sabitha , Chakraborty Apurba 
Published: March 2015

Summary We assessed the barriers and facilitators to highly active antiretroviral therapy adherence and determined their prevalence among HIV/AIDS patients in Hyderabad, India. We conducted a cross-sectional study among HIV-infected adults prescribed highly active antiretroviral therapy and receiving care from nine clinics. Depression was screened using Patient Health Questionnaire 9 and facilitators of HIV medication adherence were assessed using an 11-item scale which yielded a total positive attitude to disease score. Prevalence ratios of non-adherence between different categories of potential risk factors were calculated. We compared mean ‘facilitators to adherence’ scores between the adherent and non-adherent population. Multivariable Poisson regression with robust variance was used to identify independent risk factors. Among the 211 respondents, nearly 20% were non-adherent, approximately 8% had either moderately severe or severe depression and mean score for combined facilitators to medication adherence was 33.35 (±7.88) out of a possible 44 points. Factors significantly associated with non-adherence included older age, female sex worker, moderate-to-severe depression and the combined facilitators to medication adherence score. These data from a broad range of clinical settings in Hyderabad reveal that key groups to focus on for adherence intervention are female sex workers, older persons and those with depression.
The use of focus groups as a basis for planning and implementing culturally appropriate health promotion among people with diabetes in the Arab community
Authors: Levin-Zamir Diane , Badarne Siham , Najami Muhamed , Gan Noy Shosh , Poraz Irit , Shapira Menachem , Lieberman Nicky , Goldfracht Margalit 
Published: March 2015

Objective: The main study objective was to identify perceived barriers to achieving glycemic control among the Arab population in Israel, by both members of the Arab community with type 2 diabetes and by primary care teams working with the Arab community. Methods: A series of six focus groups using qualitative research methodology were conducted in two phases among people with diabetes and primary care professionals treating them. Results: The perception of the disease among people with diabetes was one of low severity. Barriers to adopting a healthy lifestyle and to self-management included awareness of the need, financial considerations regarding medication, and traditional gender roles. Food preparation in family life was identified as a strong cultural determinant. The health literacy needs for more in-depth and accessible educational programs were identified. Primary care staff viewed the needs similarly, with the exception of the need for in-depth instructional materials. Conclusion and practice implications: The understanding of the significance of healthy lifestyles and self-management was essential for developing culturally appropriate implementation programs and policy. Consultation with, and involvement of patient groups in needs assessment and planning is essential and should be established in policy that promotes best practice and health promotion in chronic illness.
Addition of a Gastrointestinal Microbiome Modulator to Metformin Improves Metformin Tolerance and Fasting Glucose Levels
Authors: Burton Jeffrey H. , Johnson Matthew , Johnson Jolene , Hsia Daniel S. , Greenway Frank L. , Heiman Mark L. 
Published: March 2015

Background: Adverse effects of metformin are primarily related to gastrointestinal (GI) intolerance that could limit titration to an efficacious dose or cause discontinuation of the medication. Because some metformin side effects may be attributable to shifts in the GI microbiome, we tested whether a GI microbiome modulator (GIMM) used in combination with metformin would ameliorate the GI symptoms. Methods: A 2-period crossover study design was used with 2 treatment sequences, either placebo in period 1 followed by GIMM in period 2 or vice versa. Study periods lasted for 2 weeks, with a 2-week washout period between. During the first week, type 2 diabetes patients (T2D) who experienced metformin GI intolerance took 500 mg metformin along with their assigned NM504 (GIMM) or placebo treatment with breakfast and with dinner. In the second week, the 10 subjects took 500 mg metformin (t.i.d.), with GIMM or placebo consumed with the first and third daily metformin doses. Subjects were permitted to discontinue metformin dosing if it became intolerable. Results: The combination of metformin and GIMM treatment produced a significantly better tolerance score to metformin than the placebo combination (6.78 ± 0.65 [mean ± SEM] versus 4.45 ± 0.69, P = .0006). Mean fasting glucose levels were significantly ( P < .02) lower with the metformin–GIMM combination (121.3 ± 7.8 mg/dl) than with metformin-placebo (151.9 ± 7.8 mg/dl). Conclusion: Combining a GI microbiome modulator with metformin might allow the greater use of metformin in T2D patients and improve treatment of the disease.
SWI enhances vein detection using gadolinium in multiple sclerosis
Authors: Maggi Pietro , Mazzoni Lorenzo N , Moretti Marco , Grammatico Matteo , Chiti Stefano , Massacesi Luca 
Published: March 2015

Susceptibility weighted imaging (SWI) combined with the FLAIR sequence provides the ability to depict in vivo the perivenous location of inflammatory demyelinating lesions – one of the most specific pathologic features of multiple sclerosis (MS). In addition, in MS white matter (WM) lesions, gadolinium-based contrast media (CM) can increase vein signal loss on SWI. This report focuses on two cases of WM inflammatory lesions enhancing on SWI images after CM injection. In these lesions in fact the CM increased the contrast between the parenchyma and the central vein allowing as well, in one of the two cases, the detection of a vein not visible on the same SWI sequence acquired before CM injection.
Retinoic acid and arsenic trioxide trigger degradation of mutated NPM1, resulting in apoptosis of AML cells
Authors: El Hajj Hiba , Dassouki Zeina , Berthier Caroline , Raffoux Emmanuel , Ades Lionel , Legrand Olivier , Hleihel Rita , Sahin Umut , Tawil Nadim , Salameh Ala , Zibara Kazem , Darwiche Nadine , Mohty Mohamad , Dombret Hervé , Fenaux Pierre , de Thé Hugues , Bazarbachi Ali 
Published: March 2015

Key Points
RA/arsenic induces proteasomal degradation of mutant NPM1, yielding AML growth arrest and apoptosis. RA/arsenic treatment restored nucleolar localization of NPM1 and significantly reduced bone marrow blasts in NPM1 mutant AML patients.
Fixed points of multivalued mappings in modular function spaces with a graph
Authors: Alfuraidan Monther Rashed 
Published: March 2015

AbstractLet $\rho\in\Re$
ρ
∈
ℜ
(the class of all nonzero regular function modulars defined on a nonempty set Ω) and G be a directed graph defined on a subset C of $L_{\rho}$

L
ρ

. In this paper, we discuss the existence of fixed points of monotone G-contraction and G-nonexpansive mappings in modular function spaces. These results are the modular version of Jachymski fixed point results for mappings defined in a metric space endowed with a graph.
High-precision scanning transmission electron microscopy at coarse pixel sampling for reduced electron dose
Authors: Yankovich Andrew B , Berkels Benjamin , Dahmen Wolfgang , Binev Peter , Voyles Paul M 
Published: March 2015

Abstract
Determining the precise atomic structure of materials’ surfaces, defects, and interfaces is important to help provide the connection between structure and important materials’ properties. Modern scanning transmission electron microscopy (STEM) techniques now allow for atomic resolution STEM images to have down to sub-picometer precision in locating positions of atoms, but these high-precision techniques generally require large electron doses, making them less useful for beam-sensitive materials. Here, we show that 1- to 2-pm image precision is possible by non-rigidly registering and averaging a high-angle dark field image series of a 5- to 6-nm Au nanoparticle even though a very coarsely sampled image and decreased exposure time was used to minimize the electron dose. These imaging conditions minimize the damage to the nanoparticle and capture the whole nanoparticle in the same image. The high-precision STEM image reveals bond length contraction around the entire nanoparticle surface, and no bond length variation along a twin boundary that separates the nanoparticle into two grains. Surface atoms at the edges and corners exhibit larger bond length contraction than atoms near the center of surface facets.
Role for NOD2 in Mycobacterium tuberculosis-induced iNOS expression and NO production in human macrophages
Authors: Landes Michelle B , Rajaram Murugesan V S , Nguyen Huy , Schlesinger Larry S 
Published: March 2015

Abstract
M.tb, which causes TB, is a host-adapted intracellular pathogen of macrophages. Macrophage intracellular PRRs, such as NOD proteins, regulate proinflammatory cytokine production in response to various pathogenic organisms. We demonstrated previously that NOD2 plays an important role in controlling the inflammatory response and viability of M.tb and Mycobacterium bovis BCG in human macrophages. Various inflammatory mediators, such as cytokines, ROS, and RNS, such as NO, can mediate this control. iNOS (or NOS2) is a key enzyme for NO production and M.tb control during infection of mouse macrophages; however, the role of NO during infection of human macrophages remains unclear, in part, as a result of the low amounts of NO produced in these cells. Here, we tested the hypothesis that activation of NOD2 by its ligands (MDP and GMDP, the latter from M.tb) plays an important role in the expression and activity of iNOS and NO production in human macrophages. We demonstrate that M.tb or M. bovis BCG infection enhances iNOS expression in human macrophages. The M.tb-induced iNOS expression and NO production are dependent on NOD2 expression during M.tb infection. Finally, NF-κB activation is required for NOD2-dependent expression of iNOS in human macrophages. Our data provide evidence for a new molecular pathway that links activation of NOD2, an important intracellular PRR, and iNOS expression and activity during M.tb infection of human macrophages.
Diffuse Large B-Cell Lymphoma Classification System That Associates Normal B-Cell Subset Phenotypes With Prognosis
Authors: Dybkær Karen , Bøgsted Martin , Falgreen Steffen , Bødker Julie S. , Kjeldsen Malene K. , Schmitz Alexander , Bilgrau Anders E. , Xu-Monette Zijun Y. , Li Ling , Bergkvist Kim S. , Laursen Maria B. , Rodrigo-Domingo Maria , Marques Sara C. , Rasmussen Sophie B. , Nyegaard Mette , Gaihede Michael , Møller Michael B. , Samworth Richard J. , Shah Rajen D. , Johansen Preben , El-Galaly Tarec C. , Young Ken H. , Johnsen Hans E. 
Published: March 2015

PurposeCurrent diagnostic tests for diffuse large B-cell lymphoma use the updated WHO criteria based on biologic, morphologic, and clinical heterogeneity. We propose a refined classification system based on subset-specific B-cell–associated gene signatures (BAGS) in the normal B-cell hierarchy, hypothesizing that it can provide new biologic insight and diagnostic and prognostic value.Patients and MethodsWe combined fluorescence-activated cell sorting, gene expression profiling, and statistical modeling to generate BAGS for naive, centrocyte, centroblast, memory, and plasmablast B cells from normal human tonsils. The impact of BAGS-assigned subtyping was analyzed using five clinical cohorts (treated with cyclophosphamide, doxorubicin, vincristine, and prednisone [CHOP], n = 270; treated with rituximab plus CHOP [R-CHOP], n = 869) gathered across geographic regions, time eras, and sampling methods. The analysis estimated subtype frequencies and drug-specific resistance and included a prognostic meta-analysis of patients treated with first-line R-CHOP therapy.ResultsSimilar BAGS subtype frequencies were assigned across 1,139 samples from five different cohorts. Among R-CHOP–treated patients, BAGS assignment was significantly associated with overall survival and progression-free survival within the germinal center B-cell–like subclass; the centrocyte subtype had a superior prognosis compared with the centroblast subtype. In agreement with the observed therapeutic outcome, centrocyte subtypes were estimated as being less resistant than the centroblast subtype to doxorubicin and vincristine. The centroblast subtype had a complex genotype, whereas the centrocyte subtype had high TP53 mutation and insertion/deletion frequencies and expressed LMO2, CD58, and stromal-1–signature and major histocompatibility complex class II–signature genes, which are known to have a positive impact on prognosis.ConclusionFurther development of a diagnostic platform using BAGS-assigned subtypes may allow pathogenetic studies to improve disease management.
Scalable Rejection Sampling for Bayesian Hierarchical Models
Authors: Braun Michael , Damien Paul 
Published: March 2015

Bayesian hierarchical modeling is a popular approach to capturing unobserved heterogeneity across individual units. However, standard estimation methods such as Markov chain Monte Carlo (MCMC) can be impracticable for modeling outcomes from a large number of units. We develop a new method to sample from posterior distributions of Bayesian models, without using MCMC. Samples are independent, so they can be collected in parallel, and we do not need to be concerned with issues like chain convergence and autocorrelation. The algorithm is scalable under the weak assumption that individual units are conditionally independent, making it applicable for large data sets. It can also be used to compute marginal likelihoods.Data, as supplemental material, are available at http://dx.doi.org/10.1287/mksc.2014.0901 .
Transparent Reporting of Data Quality in Distributed Data Networks
Authors: Kahn Michael G. , Brown Jeffrey S. , Chun Alein T. , Davidson Bruce N. , Meeker Daniella , Ryan Patrick B. , Schilling Lisa M. , Weiskopf Nicole G. , Williams Andrew E. , Zozus Meredith Nahm 
Published: March 2015

Introduction: Poor data quality can be a serious threat to the validity and
generalizability of clinical research findings. The growing availability of electronic
administrative and clinical data is accompanied by a growing concern about the quality
of these data for observational research and other analytic purposes. Currently, there
are no widely accepted guidelines for reporting quality results that would enable
investigators and consumers to independently determine if a data source is fit for use
to support analytic inferences and reliable evidence generation.Model and Methods: We
developed a conceptual model that captures the flow of data from data originator across
successive data stewards and finally to the data consumer. This “data lifecycle” model
illustrates how data quality issues can result in data being returned back to previous
data custodians. We highlight the potential risks of poor data quality on clinical
practice and research results. Because of the need to ensure transparent reporting of a
data quality issues, we created a unifying data-quality reporting framework and a
complementary set of 20 data-quality reporting recommendations for studies that use
observational clinical and administrative data for secondary data analysis. We obtained
stakeholder input on the perceived value of each recommendation by soliciting public
comments via two face-to-face meetings of informatics and comparative-effectiveness
investigators, through multiple public webinars targeted to the health services research
community, and with an open access online wiki.Recommendations: Our recommendations
propose reporting on both general and analysis-specific data quality features. The goals
of these recommendations are to improve the reporting of data quality measures for
studies that use observational clinical and administrative data, to ensure transparency
and consistency in computing data quality measures, and to facilitate best practices and
trust in the new clinical discoveries based on secondary use of observational
data.
Patients, Consumers, and Caregivers: The Original Data Stewards
Authors: Mackay Erin A. 
Published: March 2015

Introduction: For patients and families, the issue of data quality is personal.
When treatment decisions or research conclusions are based on incomplete or inaccurate
information—a misdiagnosis, an incomplete medication list, the wrong demographic data—
care safety, quality, and outcomes suffer—and patients and families suffer.Opportunity
for Change: Thanks in part to the power of health information technology, individuals
have new opportunities to be part of the solution when it comes to assessing and
improving data quality. Building on a framework for data quality, there are numerous
opportunities for patients to be part of ‘feedback loops’ to understand and improve data
quality are presented.Foundation for the Future: As the source of patient-centered data,
consumers have important roles to play in reviewing and confirming their own health
information and should be engaged partners in efforts to understand and improve the
quality of electronic health data.This commentary is written in response to "Transparent
Reporting of Data Quality in Distributed Data Networks” (Kahn et al.) and builds on
recommendations outlined in the framework.
Industry associations, health innovation systems and politics of development: the cases of India and South Africa
Authors: Papaioannou Theo , Watkins Andrew , Kale Dinar , Mugwagwa Julius 
Published: March 2015

AbstractOver the last 20 years, developing countries have witnessed the increased role of non-governmental actors such as health industry associations and umbrella organizations in the diffusion and governance of health innovation. Utilizing extensive interviews with actors in the Indian and South African health industries, this paper argues that, in a context of emerging pluralism – i.e., a dynamic context of bargaining between competing (public and private) interests and values – these associations constitute public actors that play dual roles in the politics of innovation and development. Specifically, not only do they engage downstream by diffusing knowledge to their respective health innovation systems in order to achieve common objectives, they also engage upstream with their governments to co-develop policies and regulations. This dual role of health industry associations and umbrella organizations makes them less neutral politically but more effective institutionally, and their innovative and political role should be seriously taken into account in the healthcare sector.
Secretory sphingomyelinase in health and disease
Authors: Kornhuber Johannes , Rhein Cosima , Müller Christian P. , Mühle Christiane 
Published: March 2015

AbstractAcid sphingomyelinase (ASM), a key enzyme in sphingolipid metabolism, hydrolyzes sphingomyelin to ceramide and phosphorylcholine. In mammals, the expression of a single gene,SMPD1,results in two forms of the enzyme that differ in several characteristics. Lysosomal ASM (L-ASM) is located within the lysosome, requires no additional Zn2+ions for activation and is glycosylated mainly with high-mannose oligosaccharides. By contrast, the secretory ASM (S-ASM) is located extracellularly, requires Zn2+ions for activation, has a complex glycosylation pattern and has a longerin vivohalf-life. In this review, we summarize current knowledge regarding the physiology and pathophysiology of S-ASM, including its sources and distribution, molecular and cellular mechanisms of generation and regulation and relevantin vitroandin vivostudies. Polymorphisms or mutations ofSMPD1lead to decreased S-ASM activity, as detected in patients with Niemann-Pick disease B. Thus, lower serum/plasma activities of S-ASM are trait markers. No genetic causes of increased S-ASM activity have been identified. Instead, elevated activity is the result of enhanced release (e.g., induced by lipopolysaccharide and cytokine stimulation) or increased enzyme activation (e.g., induced by oxidative stress). Increased S-ASM activity in serum or plasma is a state marker of a wide range of diseases. In particular, high S-ASM activity occurs in inflammation of the endothelium and liver. Several studies have demonstrated a correlation between S-ASM activity and mortality induced by severe inflammatory diseases. Serial measurements of S-ASM reveal prolonged activation and, therefore, the measurement of this enzyme may also provide information on past inflammatory processes. Thus, S-ASM may be both a promising clinical chemistry marker and a therapeutic target.
The pseudo-atomic structure of an RND-type tripartite multidrug efflux pump
Authors: Du Dijun , Voss Jarrod , Wang Zhao , Chiu Wah , Luisi Ben F. 
Published: March 2015

Abstract
Microorganisms encode several classes of transmembrane molecular pumps that can expel a wide range of chemically distinct toxic substances. These machines contribute to the capacity of the organisms to withstand harsh environments, and they help to confer resistance against clinical antimicrobial agents. In Gram-negative bacteria, some of the pumps comprise tripartite assemblies that actively transport drugs and other harmful compounds across the cell envelope. We describe recent structural and functional data that have provided insights into the architecture and transport mechanism of the AcrA-AcrB-TolC pump of Escherichia coli. This multidrug efflux pump is powered by proton electrochemical gradients through the activity of AcrB, a member of the resistance/nodulation/cell division (RND) transporter family. Crystallographic data reveal how the small protein AcrZ binds to AcrB in a concave surface of the transmembrane domain, and we discuss how this interaction may affect the efflux activities of the transporter.