bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combined use of fractional exhaled nitric oxide and bronchodilator response in predicting future loss of asthma control among children with atopic asthma
Authors: Kim Je‐Kyung , Jung Jae‐Yub , Kim Heon , Eom Sang‐Yong , Hahn Youn‐Soo 
Published: October 2016

ABSTRACT
Background and objectiveRecognition of patients at risk of asthma exacerbation is important for future asthma care and improved outcome. The aim of the present study was to see whether measurements of bronchodilator response (BDR) and fractional exhaled nitric oxide (FeNO) in combination provide prognostic information superior to either measurement alone in children with atopic asthma.MethodsA total of 201 atopic children aged 8–16 years with intermittent or mild persistent asthma were included. Pulmonary function tests including BDR and FeNO were serially monitored 10 times or more over 2 years when subjects were not receiving controller medications. After completion of monitoring, 1‐year observation for a loss of asthma control was performed.ResultsDuring the monitoring period, positive BDRs (≥12% in forced expiratory volume in 1 s (FEV1
) from pre‐bronchodilator value) and FeNO higher than 35 parts per billion (ppb) were observed at least once in 59% and 77% of participants. When analysed as continuous variables, both BDR (hazard ratio (HR): 1.21; 95% CI: 1.04–1.41; P = 0.014) and FeNO (HR: 1.27; 95% CI: 1.09–1.49; P = 0.003) were associated with increased risks for a control loss. Compared with patients showing either positive BDRs (HR: 3.19; 95% CI: 1.05–9.64) or FeNO higher than 35 ppb (HR: 4.70; 95% CI: 1.68–13.11), patients with both findings (HR: 7.08; 95% CI: 2.57–19.49) had greater risks for a control loss.ConclusionThese data support that combined use of BDR and FeNO measurements can modify predictive risk obtained from either measurement alone.
(De)familialization and (De)genderization – Competing or Complementary Perspectives in Comparative Policy Analysis?
Authors: Kurowska Anna 
Published: October 2016

AbstractThis article critically engages with Saxonberg's proposal (2013) to replace the (de)familialization perspective with the (de)genderization approach in comparative family policy/regime studies. It argues: (1) there is a need to refine the term ‘(de)familialization’ and to bring in the child's and elderly's perspective; (2) the ‘(de)familialization’ and ‘(de)genderization’ perspectives are mutually irreplaceable; and (3) there is a need to conceptualize the theoretical relationship between these two perspectives. The article further proposes to use the theoretical framework of Amartya Sen's Capability Approach (CA) to reinterpret both analytical perspectives with a dual advantage using that approach would lend. It first conceptualizes the de‐familializing and de‐genderizing policies as ‘means’ designed to increase peoples' ‘capabilities’ to achieve ‘valued functionings’ and not ultimate goals of policies that aim to change people's ‘functionings’. Thus, it addresses the criticism of de‐familialization and de‐genderization as policy strategies that enforce certain, potentially controversial ideals of societal and familial relations. Second, by using crucial CA concepts, i.e. ‘means’, ‘capabilities’ and ‘functionings’, it refines the interpretation of policy‐, regime‐ and outcome‐oriented analyses (typologies). As a result, it clarifies the distinction between these types of analyses and highlights the advantages of both a policy approach and a redefined regime approach.
Interests groups in Parliament: Exploring MPs’ interest affiliations (2000‐2011)
Authors: Gava Roy , Varone Frédéric , Mach André , Eichenberger Steven , Christe Julien , Chao‐Blanco Corinne 
Published: October 2016

AbstractThis research note presents an innovative dataset of Swiss MPs’ interest ties between 2000‐2011. The longitudinal analysis shows that the average number of interest ties per MP has more than doubled: from 3.5 in 2000 to 7.6 in 2011. Since the mid‐2000s, public interest groups have accounted for approximately one out of two ties between MPs and interest groups, showing the strongest increase during the period. However, when looking at the most present individual groups, important business groups dominate and appear well connected with the governmental parties of the political right. Finally, interest groups are also able to forge themselves a strategic presence within the parliamentary committees that are the most relevant for their policy issues. Next research steps include the assessment of the (un)biased access of interest groups to the parliamentary venue and their policy influence.
Strategi Menangani Kemelut Golongan Anti Hadis (GAH)
Authors: Ghazali Mohd Al’Ikhsan , Md. Sawari Siti Salwa , Al-Hafiz Muhaidi Mustaffa , Rashid Mohd Hambali 
Published: October 2016

Penyebaran pemikiran anti hadis di Malaysia kini semakin membimbangkan. Sektor pendidikan juga turut terkesan daripada bahang pemikiran sesat ini. Umat Islam sepatutnya menyedari bahawa pemikiran ini telah cuba merosak Islam secara keseluruhannya. Mereka telah berjaya melatih kader-kader di kalangan cendekiawan Islam sendiri dalam usaha merealisasikan pemikiran mereka. Demi menjaga kesucian Islam, pemikiran anti hadis ini haruslah di hapuskan. Oleh itu tujuan kajian ini dilaksanakan bagi mengenal pasti langkah-langkah penyelesaian yang telah diamalkan oleh pelbagai pihak di Malaysia. Metode kajian perpustakaan dan temu bual telah digunakan oleh pengkaji bagi menyelesaikan permasalahan kajian ini. Di dalam kajian ini, pengkaji telah menemui pelbagai langkah-langkah pembanterasan dan penyelesaian bagi kemelut pemikiran anti hadis yang mana telah dilaksanakan oleh pihak berkuasa dan masyarakat sendiri. Dapatan daripada kajian boleh menjadi garis panduan dalam memaksimumkan pembanterasan kemelut Golongan Anti Hadis daripada tersebar luar. Bukan itu sahaja kajian ini di harapkan dapat membantu para ahli akademik untuk mengenalpasti kesan-kesan penyelesain yang telah terlaksana.
Identification of a New Lipoprotein Export Signal in Gram-Negative Bacteria
Authors: Lauber Frédéric , Cornelis Guy Richard , Renzi Francesco 
Published: October 2016

ABSTRACT

Bacteria of the phylum
Bacteroidetes
, including commensal organisms and opportunistic pathogens, harbor abundant surface-exposed multiprotein membrane complexes (Sus-like systems) involved in carbohydrate acquisition. These complexes have been mostly linked to commensalism, and in some instances, they have also been shown to play a role in pathogenesis. Sus-like systems are mainly composed of lipoproteins anchored to the outer membrane and facing the external milieu. This lipoprotein localization is uncommon in most studied Gram-negative bacteria, while it is widespread in
Bacteroidetes
. Little is known about how these complexes assemble and particularly about how lipoproteins reach the bacterial surface. Here, by bioinformatic analyses, we identify a lipoprotein export signal (LES) at the N termini of surface-exposed lipoproteins of the human pathogen
Capnocytophaga canimorsus
corresponding to K-(D/E)
2
or Q-A-(D/E)
2
. We show that, when introduced in sialidase SiaC, an intracellular lipoprotein, this signal is sufficient to target the protein to the cell surface. Mutational analysis of the LES in this reporter system showed that the amino acid composition, position of the signal sequence, and global charge are critical for lipoprotein surface transport. These findings were further confirmed by the analysis of the LES of mucinase MucG, a naturally surface-exposed
C. canimorsus
lipoprotein. Furthermore, we identify a LES in
Bacteroides fragilis
and
Flavobacterium johnsoniae
surface lipoproteins that allow
C. canimorsus
surface protein exposure, thus suggesting that
Bacteroidetes
share a new bacterial lipoprotein export pathway that flips lipoproteins across the outer membrane.

IMPORTANCE
Bacteria of the phylum
Bacteroidetes
are important human commensals and pathogens. Understanding their biology is therefore a key question for human health. A main feature of these bacteria is the presence of abundant lipoproteins at their surface that play a role in nutrient acquisition. To date, the underlying mechanism of lipoprotein transport is unknown. We show for the first time that
Bacteroidetes
surface lipoproteins share an N-terminal signal that drives surface localization. The localization and overall negative charge of the lipoprotein export signal (LES) are crucial for its role. Overall, our findings provide the first evidence that
Bacteroidetes
are endowed with a new bacterial lipoprotein export pathway that flips lipoproteins across the outer membrane.
Release of gp120 Restraints Leads to an Entry-Competent Intermediate State of the HIV-1 Envelope Glycoproteins
Authors: Herschhorn Alon , Ma Xiaochu , Gu Christopher , Ventura John D. , Castillo-Menendez Luis , Melillo Bruno , Terry Daniel S. , Smith Amos B. , Blanchard Scott C. , Munro James B. , Mothes Walther , Finzi Andrés , Sodroski Joseph 
Published: October 2016

ABSTRACT

Primary human immunodeficiency virus (HIV-1) envelope glycoprotein (Env) trimers [(gp120/gp41)
3
] typically exist in a metastable closed conformation (state 1). Binding the CD4 receptor triggers Env to undergo extensive conformational changes to mediate virus entry. We identified specific gp120 residues that restrain Env in state 1. Alteration of these restraining residues destabilized state 1, allowing Env to populate a functional conformation (state 2) intermediate between state 1 and the full CD4-bound state (state 3). Increased state 2 occupancy was associated with lower energy barriers between the states. State 2 was an obligate intermediate for all transitions between state 1 and state 3. State 2-enriched Envs required lower CD4 concentrations to trigger virus entry and more efficiently infected cells expressing low levels of CD4. These Envs were resistant to several broadly neutralizing antibodies and small-molecule inhibitors. Thus, state 2 is an Env conformation on the virus entry pathway; sampling state 2 increases the adaptability of HIV-1 to different host cell receptor levels and immune environments. Our results provide new insights into the conformational regulation of HIV-1 entry.

IMPORTANCE
The envelope glycoproteins (Env) of HIV-1 mediate virus entry and are the sole targets of neutralizing antibodies. Understanding the way that Env promotes HIV-1 entry can expedite drug and vaccine development. By destabilizing Env, we found that it assumes an intermediate state that is functional and obligate for transitions to entry-competent conformations. Increased sampling of this state enhances the ability of HIV-1 to infect cells that express low levels of the CD4 receptor and allows the virus to evade neutralizing antibodies and small-molecule inhibitors. These findings provide new mechanistic insights into the function and inhibition of HIV-1 Env and will contribute to ongoing therapeutic and prevention efforts to combat HIV-1.
Pharmacological Inhibition of Host Heme Oxygenase-1 Suppresses Mycobacterium tuberculosis Infection
In Vivo
by a Mechanism Dependent on T Lymphocytes
Authors: Costa Diego L. , Namasivayam Sivaranjani , Amaral Eduardo P. , Arora Kriti , Chao Alex , Mittereder Lara R. , Maiga Mamoudou , Boshoff Helena I. , Barry Clifton E. , Goulding Celia W. , Andrade Bruno B. , Sher Alan 
Published: October 2016

ABSTRACT

Heme oxygenase-1 (HO-1) is a stress response antioxidant enzyme which catalyzes the degradation of heme released during inflammation. HO-1 expression is upregulated in both experimental and human
Mycobacterium tuberculosis
infection, and in patients it is a biomarker of active disease. Whether the enzyme plays a protective versus pathogenic role in tuberculosis has been the subject of debate. To address this controversy, we administered tin protoporphyrin IX (SnPPIX), a well-characterized HO-1 enzymatic inhibitor, to mice during acute
M. tuberculosis
infection
.
These SnPPIX-treated animals displayed a substantial reduction in pulmonary bacterial loads comparable to that achieved following conventional antibiotic therapy. Moreover, when administered adjunctively with antimycobacterial drugs, the HO-1 inhibitor markedly enhanced and accelerated pathogen clearance. Interestingly, both the pulmonary induction of HO-1 expression and the efficacy of SnPPIX treatment in reducing bacterial burden were dependent on the presence of host T lymphocytes. Although
M. tuberculosis
expresses its own heme-degrading enzyme, SnPPIX failed to inhibit its enzymatic activity or significantly restrict bacterial growth in liquid culture. Together, the above findings reveal mammalian HO-1 as a potential target for host-directed monotherapy and adjunctive therapy of tuberculosis and identify the immune response as a critical regulator of this function.

IMPORTANCE
There is no reliable vaccine against tuberculosis (TB), and conventional antibiotic therapy is administered over at least 6 months. This prolonged treatment period can lead to noncompliance resulting in relapsed infection as well as the emergence of multidrug resistance. Thus, there is an urgent need for improved therapeutic regimens that can more rapidly and efficiently control
M. tuberculosis
in infected patients. Here, we describe a potential strategy for treating TB based on pharmacological inhibition of the host heme-degrading enzyme HO-1. This approach results in significantly reduced bacterial burdens in mice, and when administered in conjunction with conventional antibiotic therapy, leads to faster, more effective pathogen clearance without detectable direct effects on the mycobacteria themselves. Interestingly, the effects of HO-1 inhibition on
M. tuberculosis
infection
in vivo
are dependent on the presence of an intact host immune system. These observations establish mammalian HO-1 as a potential target for host-directed therapy of TB.
Quorum Quenching of Nitrobacter winogradskyi Suggests that Quorum Sensing Regulates Fluxes of Nitrogen Oxide(s) during Nitrification
Authors: Mellbye Brett L. , Giguere Andrew T. , Bottomley Peter J. , Sayavedra-Soto Luis A. 
Published: October 2016

ABSTRACT

Quorum sensing (QS) is a widespread process in bacteria used to coordinate gene expression with cell density, diffusion dynamics, and spatial distribution through the production of diffusible chemical signals. To date, most studies on QS have focused on model bacteria that are amenable to genetic manipulation and capable of high growth rates, but many environmentally important bacteria have been overlooked. For example, representatives of proteobacteria that participate in nitrification, the aerobic oxidation of ammonia to nitrate via nitrite, produce QS signals called acyl-homoserine lactones (AHLs). Nitrification emits nitrogen oxide gases (NO, NO
2
, and N
2
O), which are potentially hazardous compounds that contribute to global warming. Despite considerable interest in nitrification, the purpose of QS in the physiology/ecology of nitrifying bacteria is poorly understood. Through a quorum quenching approach, we investigated the role of QS in a well-studied AHL-producing nitrite oxidizer,
Nitrobacter winogradskyi
. We added a recombinant AiiA lactonase to
N. winogradskyi
cultures to degrade AHLs to prevent their accumulation and to induce a QS-negative phenotype and then used mRNA sequencing (mRNA-Seq) to identify putative QS-controlled genes. Our transcriptome analysis showed that expression of
nirK
and
nirK
cluster genes (
ncgABC
) increased up to 19.9-fold under QS-proficient conditions (minus active lactonase). These data led to us to query if QS influenced nitrogen oxide gas fluxes in
N. winogradskyi
. Production and consumption of NO
x
increased and production of N
2
O decreased under QS-proficient conditions. Quorum quenching transcriptome approaches have broad potential to identify QS-controlled genes and phenotypes in organisms that are not genetically tractable.

IMPORTANCE
Bacterial cell-cell signaling, or quorum sensing (QS), is a method of bacterial communication and gene regulation that is well studied in bacteria. However, little is known about the purpose of QS in many environmentally important bacteria. Here, we demonstrate quorum quenching coupled with mRNA-Seq to identify QS-controlled genes and phenotypes in
Nitrobacter winogradskyi
, a nitrite-oxidizing bacterium. Nitrite oxidizers play an important role in the nitrogen cycle though their participation in nitrification, the aerobic oxidation of ammonia to nitrate via nitrite. Our quorum quenching approach revealed that QS influences production and consumption of environmentally important nitrogen oxide gases (NO, NO
2
, and N
2
O) in
N. winogradskyi
. This study demonstrated a novel technique for studying QS in difficult-to-work-with microorganisms and showed that nitrite oxidizers might also contribute to nitrification-dependent production of nitrogen oxide gases that contribute to global warming.
Supporting the provision of palliative care in the home environment: a proof-of-concept single-arm trial of a PalliativE Carers Education Package (PrECEPt)
Authors: Forbat Liz , Haraldsdottir Erna , Lewis Marsha , Hepburn Ken 
Published: October 2016

IntroductionPractical educational interventions for palliative carers are needed. Current supports frequently rely on carers travelling to a central venue to receive education. A substantial gap therefore exists around determining how high-quality relevant information can be delivered nationally, with limited cost implications, using educational methods that are acceptable to carers in palliative care. This study seeks to design and assess feasibility and acceptability of a distance-learning approach to educating carers.MethodsThis is an embedded mixed-method feasibility and acceptability study. It embeds an unblinded 1-arm pilot test, with subsequent qualitative interviews which will be used to inform the assessment of the intervention's acceptability and feasibility. The theoretical framework is self-efficacy theory, whereby we seek to impact carers' beliefs in their ability to carry out and succeed in caring tasks and situations. The educational materials focused on pain and nutrition/hydration will be developed in phase 1 with former carers (n=8) providing input into the content and style of materials. The educational package privileges adult-learning styles, recognising and responding to the learner's context including their learning needs, prior knowledge and motivations for engaging in education. The materials will be tested with up to 24 current carers.AnalysisAnalysis will focus on determining recruitment processes for a full-scale study, data collection procedures/completion rates, queries directed to the hospice from carers involved in the feasibility work, mode of delivery and content of the materials. The primary outcome measure is self-efficacy, with other measures focused on caregiver preparedness and caregiving tasks, consequences and needs questionnaire. Adherence to educational components will also be collected and reported.Ethics and disseminationEthical approval has been provided by the participating site, Calvary Healthcare, Canberra, reference 02–2016, and the Australian Catholic University. Results will be published in peer-reviewed journals, presented at conferences and a lay summary sent to participants.Trial registration numberACTRN12616000601437; Pre-results.
Rehabilitation Enablement in Chronic Heart Failure—a facilitated self-care rehabilitation intervention in patients with heart failure with preserved ejection fraction (REACH-HFpEF) and their caregivers: rationale and protocol for a single-centre pilot randomised controlled trial
Authors: Eyre V , Lang C C , Smith K , Jolly K , Davis R , Hayward C , Wingham J , Abraham C , Green C , Warren F C , Britten N , Greaves C J , Doherty P , Austin J , Van Lingen R , Singh S , Buckingham S , Paul K , Taylor R S , Dalal H M 
Published: October 2016

IntroductionThe Rehabilitation EnAblement in CHronic Heart Failure in patients with Heart Failure (HF) with preserved ejection fraction (REACH-HFpEF) pilot trial is part of a research programme designed to develop and evaluate a facilitated, home-based, self-help rehabilitation intervention to improve self-care and quality of life (QoL) in heart failure patients and their caregivers. We will assess the feasibility of a definitive trial of the REACH-HF intervention in patients with HFpEF and their caregivers. The impact of the REACH-HF intervention on echocardiographic outcomes and bloodborne biomarkers will also be assessed.Methods and analysisA single-centre parallel two-group randomised controlled trial (RCT) with 1:1 individual allocation to the REACH-HF intervention plus usual care (intervention) or usual care alone (control) in 50 HFpEF patients and their caregivers. The REACH-HF intervention comprises a REACH-HF manual with supplementary tools, delivered by trained facilitators over 12 weeks. A mixed methods approach will be used to assess estimation of recruitment and retention rates; fidelity of REACH-HF manual delivery; identification of barriers to participation and adherence to the intervention and study protocol; feasibility of data collection and outcome burden. We will assess the variance in study outcomes to inform a definitive study sample size and assess methods for the collection of resource use and intervention delivery cost data to develop the cost-effectiveness analyses framework for any future trial. Patient outcomes collected at baseline, 4 and 6 months include QoL, psychological well-being, exercise capacity, physical activity and HF-related hospitalisation. Caregiver outcomes will also be assessed, and a substudy will evaluate impact of the REACH-HF manual on resting global cardiovascular function and bloodborne biomarkers in HFpEF patients.Ethics and disseminationThe study is approved by the East of Scotland Research Ethics Service (Ref: 15/ES/0036). Findings will be disseminated via journals and presentations to clinicians, commissioners and service users.Trial registration numberISRCTN78539530; Pre-results .
Reasons and evolution of non-thrombolysis in acute ischaemic stroke
Authors: Reiff T , Michel P 
Published: October 2016

IntroductionDespite increasing evidence of its efficacy in advanced age or in mild or severe strokes, intravenous thrombolysis remains underused for acute ischaemic stroke (AIS). Our aim was to obtain an updated view of reasons for non-thrombolysis and to identify its changing patterns over time.MethodsThis is a retrospective study of prospectively collected data from the Acute Stroke Registry and Analysis of Lausanne (ASTRAL) from the years 2003–2011. Patients admitted with acute stroke in the past 24 hours who had not had thrombolysis were identified; reasons for non-thrombolysis documented in the prospectively entered data were tabulated and analysed for the group as a whole. Data were analysed for the years 2003–2006 and 2007 forward because of changes in contraindications. A subgroup of patients who arrived within the treatment window ≤180 min was separately analysed for reasons for non-thrombolysis. Predictors of non-thrombolysis were investigated via multivariate regression analyses.ResultsIn the 2019 non-thrombolysed patients the most frequent reasons for non-thrombolysis were admission delays (66.3%), stroke severity (mostly mild) (47.9%) and advanced age (14.1%); 55.9% had more than one exclusion criterion. Among patients arriving ≤180 min after onset, the main reasons were stroke severity and advanced age. After 2006, significantly fewer patients were excluded because of age (OR 2.65, p<0.001) or (mostly mild) stroke severity (OR 10.56, p=0.029). Retrospectively, 18.7% of all non-thrombolysed patients could have been treated because they only had relative contraindications.ConclusionOnset-to-admission delays remain the main exclusion criterion for thrombolysis. Among early arrivals, relative contraindications such as minor stroke severity and advanced age were frequent. Thrombolysis rate increased with the reduction of thrombolysis restrictions (eg, age and stroke severity).