bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inspiratory capacity‐to‐total lung capacity ratio and dyspnoea predict exercise capacity decline in COPD
Authors: Ramon Maria A. , Ferrer Jaume , Gimeno‐Santos Elena , Donaire‐Gonzalez David , Rodríguez Esther , Balcells Eva , de Batlle Jordi , Benet Marta , Guerra Stefano , Sauleda Jaume , Ferrer Antoni , Farrero Eva , Gea Joaquim , Barberà Joan A. , Agustí Alvar , Rodriguez‐Roisin Robert , Antó Josep M. , Garcia‐Aymerich Judith ,   PAC‐COPD Study Group
Published: December 2015

AbstractBackground and objectiveExercise capacity decline is a predictor of mortality in patients with chronic obstructive pulmonary disease (COPD). Static pulmonary hyperinflation is a key determinant of exercise performance, but its effect on the longitudinal decline in exercise capacity remains unknown. We aimed to study the relationship between the inspiratory capacity‐to‐total lung capacity (IC/TLC) ratio and exercise capacity decline in COPD.MethodsWe measured IC/TLC and other relevant clinical and functional variables in 342 clinically stable patients with COPD. The 6‐min walk distance (6MWD) was determined at recruitment and after a mean ± SD of 1.7 ± 0.3 years. The annual rate of change in 6MWD was calculated. Multiple imputation to account for losses during follow up was implemented, and multivariate regression was used to analyze predictive factors of 6MWD decline.ResultsMean decline rate in the 6MWD was 21.9 ± 34.1 m/year. In the bivariate analysis, patients with lower levels of IC/TLC had greater 6MWD decline (−27.4 ± 42.5, −24.9 ± 36.5 and −13.4 ± 39.9 m/year in the first, second and third tertile of IC/TLC, respectively; P‐for‐trend = 0.018). From other potential risk factors considered, dyspnoea, health status, serum C‐reactive protein and Borg dyspnoea score at the end of the exercise test were related to exercise capacity decline. In the multivariate regression model, only IC/TLC (β = 0.7 m/year per each percentage unit of IC/TLC; P = 0.007) and dyspnoea (mMRC ≥ 2) (β = −14.6 m/year; P = 0.013) were associated with the annual rate of 6MWD change.ConclusionIC/TLC and dyspnoea in clinically stable patients with COPD predict their exercise capacity decline and may help to guide early therapeutic interventions.
Vaccine‐Induced Antibody Responses Prevent the Induction of Interferon Type I Responses Upon a Homotypic Live Virus Challenge
Authors: Chan J. , Babb R. , David S. C. , McColl S. R. , Alsharifi M. 
Published: December 2015

AbstractDuring acute viral infections, innate immunity provides essential protective measures to minimize virus dissemination and regulate adaptive immunity. This helps to successfully eliminate the pathogen and establish long‐term memory. Here, we investigated the effect of vaccine‐induced antibody responses on the induction of IFN‐I responses and the associated lymphocyte activation using influenza A virus vaccination and challenge models. Mice were vaccinated with gamma‐irradiated influenza A virus (γ‐FLU) and challenged three weeks later with live virus. Our data show a significant reduction in IFN‐I responses and lymphocyte activation following a homotypic virus challenge. We confirmed the role of vaccine‐induced antibody responses in the observed impairment of IFN‐I and the associated lymphocyte activation using adoptive transfer of immune sera and the administration of sera‐treated viruses prior to challenge. Overall, we addressed a fundamental concept in immunology and provided experimental data illustrating the inhibition of IFN‐I responses in vaccinated animals upon a homotypic virus challenge.
Trehalose 6–phosphate coordinates organic and amino acid metabolism with carbon availability
Authors: Figueroa Carlos M. , Feil Regina , Ishihara Hirofumi , Watanabe Mutsumi , Kölling Katharina , Krause Ursula , Höhne Melanie , Encke Beatrice , Plaxton William C. , Zeeman Samuel C. , Li Zhi , Schulze Waltraud X. , Hoefgen Rainer , Stitt Mark , Lunn John E. 
Published: December 2015

SummaryTrehalose 6–phosphate (Tre6P) is an essential signal metabolite in plants, linking growth and development to carbon metabolism. The sucrose–Tre6P nexus model postulates that Tre6P acts as both a signal and negative feedback regulator of sucrose levels. To test this model, short‐term metabolic responses to induced increases in Tre6P levels were investigated in Arabidopsis thaliana plants expressing the Escherichia coli Tre6P synthase gene (otsA) under the control of an ethanol‐inducible promoter. Increased Tre6P levels led to a transient decrease in sucrose content, post‐translational activation of nitrate reductase and phosphoenolpyruvate carboxylase, and increased levels of organic and amino acids. Radio‐isotope (14CO2) and stable isotope (13CO2) labelling experiments showed no change in the rates of photoassimilate export in plants with elevated Tre6P, but increased labelling of organic acids. We conclude that high Tre6P levels decrease sucrose levels by stimulating nitrate assimilation and anaplerotic synthesis of organic acids, thereby diverting photoassimilates away from sucrose to generate carbon skeletons and fixed nitrogen for amino acid synthesis. These results are consistent with the sucrose–Tre6P nexus model, and implicate Tre6P in coordinating carbon and nitrogen metabolism in plants.
Allium telomeres unmasked: the unusual telomeric sequence (CTCGGTTATGGG)n is synthesized by telomerase
Authors: Fajkus Petr , Peška Vratislav , Sitová Zdeňka , Fulnečková Jana , Dvořáčková Martina , Gogela Roman , Sýkorová Eva , Hapala Jan , Fajkus Jiří 
Published: December 2015

SummaryPhylogenetic divergence in Asparagales plants is associated with switches in telomere sequences. The last switch occurred with divergence of the genus Allium (Amaryllidaceae) from the other Allioideae (formerly Alliaceae) genera, resulting in uncharacterized telomeres maintained by an unknown mechanism. To characterize the unknown Allium telomeres, we applied a combination of bioinformatic processing of transcriptomic and genomic data with standard approaches in telomere biology such as BAL31 sensitivity tests, terminal restriction fragment analysis, the telomere repeat amplification protocol (TRAP), and fluorescence in situ hybridization (FISH). Using these methods, we characterize the unusual telomeric sequence (CTCGGTTATGGG)n present in Allium species, demonstrate its synthesis by telomerase, and characterize the telomerase reverse transcriptase (TERT) subunit of Allium cepa. Our findings open up the possibility of studying the molecular details of the evolutionary genetic change in Allium telomeres and its possible role in speciation. Experimental studies addressing the implications of this change in terms of the interplay of telomere components may now be designed to shed more light on telomere functions and evolution in general.
Evaluation of hematologic variables in newborn C57/BL6 mice up to day 35
Authors: White Jessica R. , Gong Huiyu , Colaizy Tarah T. , Moreland Jessica G. , Flaherty Heather , McElroy Steven J. 
Published: December 2015

BackgroundHematologic variables are often analyzed in animal analogs during the investigation of complex disease etiologies such as necrotizing enterocolitis. However, reference intervals (RI) can vary depending on animal strain, age, and sampling site. Reference intervals have been published for adult C57BL/6J mice, but not newborn C57BL/6J mice.ObjectivesThe purpose of the present study was to determine hematologic RI in newborn C57BL/6J mice up to day 35.MethodsC57BL/6J mice founders from The Jackson Laboratory were bred at the University of Iowa. Blood samples were obtained via facial vein sampling at postnatal days 0 (p0), p7, p14, p21, p28, or young adulthood (p35). CBCs were determined with the Sysmex XT‐2000iV analyzer within 30 minutes of blood collection at a 1:10 dilution. Statistics were determined using nonparametric methods following ASVCP guidelines.ResultsHematologic RI were determined for each of the 6 groups (n = 247, n ≥ 39 per group). Significantly higher values for HGB, RBC, and PLT counts were observed with advancing developmental age. Total WBC counts remained relatively stable during the first 35 days of life. However, WBC differential counts were dominated by neutrophils and lymphocytes in the younger mice, with a trend toward a lymphocytic leukogram on day 35.ConclusionsThese results illustrate the dynamic changes in hematologic variables during murine development after birth. Utilization of age‐specific RI is advised when evaluating data derived from experimental perinatal mouse models.
Development of an Anti-Elicitin Antibody-Based Immunohistochemical Assay for Diagnosis of Pythiosis
Authors: Inkomlue Ruchuros , Larbcharoensub Noppadol , Karnsombut Patcharee , Lerksuthirat Tassanee , Aroonroch Rangsima , Lohnoo Tassanee , Yingyong Wanta , Santanirand Pitak , Sansopha Lalana , Krajaejun Theerapong 
Published: December 2015

ABSTRACT

Pythiosis is an emerging and life-threatening infectious disease of humans and animals living in tropical and subtropical countries and is caused by the fungus-like organism
Pythium insidiosum
. Antifungals are ineffective against this pathogen. Most patients undergo surgical removal of the infected organ, and many die from advanced infections. Early and accurate diagnosis leads to prompt management and promotes better prognosis for affected patients. Immunohistochemical assays (IHCs) have been developed using rabbit antibodies raised against
P. insidiosum
crude extract, i.e., culture filtrate antigen (CFA), for the histodiagnosis of pythiosis, but cross-reactivity with pathogenic fungi compromises the diagnostic performance of the IHC. Therefore, there is a need to improve detection specificity. Recently, the elicitin protein, ELI025, was identified in
P. insidiosum
, but it was not identified in other human pathogens, including true fungi. The ELI025-encoding gene was successfully cloned and expressed as a recombinant protein in
Escherichia coli
. This study aims to develop a new IHC using the rabbit anti-ELI025 antibody (anti-ELI) and to compare its performance with the previously reported anti-CFA-based IHC. Thirty-eight
P. insidiosum
histological sections stained positive by anti-ELI-based and anti-CFA-based IHCs indicating 100% detection sensitivity for the two assays. The anti-ELI antibody stained negative for all 49 negative-control sections indicating 100% detection specificity. In contrast, the anti-CFA antibody stained positive for one of the 49 negative controls (a slide prepared from
Fusarium
-infected tissue) indicating 98% detection specificity. In conclusion, the anti-ELI based IHC is sensitive and specific for the histodiagnosis of pythiosis and is an improvement over the anti-CFA-based assay.
Sustainability of professionals’ adherence to clinical practice guidelines in medical care: a systematic review
Authors: Ament Stephanie M C , de Groot Jeanny J A , Maessen José M C , Dirksen Carmen D , van der Weijden Trudy , Kleijnen Jos 
Published: December 2015

ObjectivesTo evaluate (1) the state of the art in sustainability research and (2) the outcomes of professionals’ adherence to guideline recommendations in medical practice.DesignSystematic review.Data sourcesSearches were conducted until August 2015 in MEDLINE, CINAHL, EMBASE, Cochrane Central Register of Controlled Trials(CENTRAL) and the Guidelines International Network (GIN) library. A snowball strategy, in which reference sections of other reviews and of included papers were searched, was used to identify additional papers.Eligibility criteriaStudies needed to be focused on sustainability and on professionals’ adherence to clinical practice guidelines in medical care. Studies had to include at least 2 measurements: 1 before (PRE) or immediately after implementation (EARLY POST) and 1 measurement longer than 1 year after active implementation (LATE POST).ResultsThe search retrieved 4219 items, of which 14 studies met the inclusion criteria, involving 18 sustainability evaluations. The mean timeframe between the end of active implementation and the sustainability evaluation was 2.6 years (minimum 1.5–maximum 7.0). The studies were heterogeneous with respect to their methodology. Sustainability was considered to be successful if performance in terms of professionals’ adherence was fully maintained in the late postimplementation phase. Long-term sustainability of professionals’ adherence was reported in 7 out of 18 evaluations, adherence was not sustained in 6 evaluations, 4 evaluations showed mixed sustainability results and in 1 evaluation it was unclear whether the professional adherence was sustained.Conclusions(2) Professionals’ adherence to a clinical practice guideline in medical care decreased after more than 1 year after implementation in about half of the cases. (1) Owing to the limited number of studies, the absence of a uniform definition, the high risk of bias, and the mixed results of studies, no firm conclusion about the sustainability of professionals’ adherence to guidelines in medical practice can be drawn.
Danish register-based study on the association between specific cardiovascular drugs and fragility fractures
Authors: Torstensson Maia , Hansen Annette Højmann , Leth-Møller Katja , Jørgensen Terese Sara Høj , Sahlberg Marie , Andersson Charlotte , Kristensen Karl Emil , Ryg Jesper , Weeke Peter , Torp-Pedersen Christian , Gislason Gunnar , Holm Ellen 
Published: December 2015

ObjectiveTo determine whether drugs used in treatment of cardiovascular diseases (CVD-drugs), including hypertension, increase the risk of fragility fractures in individuals above the age of 65 years.DesignRetrospective nationwide cohort study.SettingDanish nationwide national registers.ParticipantsAll individuals in Denmark ≥65 years who used specified CVD-drugs in the study period between 1999 and 2012.Main outcomes measuresTime-dependent exposure to CVD-drugs (nitrates, digoxin, thiazides, furosemide, ACE inhibitors, angiotensin receptor antagonists, β-blockers, calcium antagonists and statins) was determined by prescription claims from pharmacies. The association between use of specific CVD-drugs and fragility fractures was assessed using multivariable Poisson regression models, and adjusted incidence rate ratios (IRRs) were calculated.ResultsOverall, 1 586 554 persons were included, of these 16.1% experienced a fall-related fracture. The multivariable Poisson regression analysis showed positive associations between fracture and treatment with furosemide, thiazide and digoxin. IRRs during the first 14 days of treatment were for furosemide IRR 1.74 (95% CI 1.61 to 1.89) and for thiazides IRR 1.41 (1.28 to 1.55); IRR during the first 30 days of treatment with digoxin was 1.18 (1.02 to 1.37).ConclusionsUse of furosemide, thiazides and digoxin was associated with elevated rates of fragility fractures among elderly individuals. This may warrant consideration when considering diuretic treatment of hypertension in elderly individuals.
Mutation screening for thalassaemia in the Jino ethnic minority population of Yunnan Province, Southwest China
Authors: Wang Shiyun , Zhang Rong , Xiang Guangxin , Li Yang , Hou Xuhong , Jiang Fusong , Jiang Feng , Hu Cheng , Jia Weiping 
Published: December 2015

ObjectivesThis study aimed to detect α- and β-thalassaemia mutations in the Jino ethnic minority population of Yunnan Province, Southwest China.DesignA total of 1613 Jino adults were continuously recruited from February 2012 to April 2012. Fasting venous blood samples were obtained to determine haematological variables. Haemoglobin analysis was conducted using high-performance liquid chromatography. Participants with hypochromic microcytic anaemia or positive haemoglobin analysis profiles were confirmed by α- and β-globin genetic testing, including DNA microarray analysis, direct sequencing methods and multiplex gap-PCR assays.SettingShanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Jiao Tong University Affiliated Sixth People's Hospital.ResultsWe found 363 suspected cases by primary screening of haematological variables and haemoglobin analysis. After further genetic testing, four types of α- and β-thalassaemia mutation were detected in 203 out of 363 individuals. Both α0- and α+-thalassaemia mutations, --SEAand -α3.7, were identified. β-Thalassaemia mutations included CD17 (HBB:c.52A>T) and CD26 (HbE or HBB:c.79G>A). In addition, 13 HbE carriers had coexisting α0- or α+-thalassaemia deletions. Clinical haematological variables indicated that, in this study, carriers of all thalassaemic genotypes had more severe hypochromic microcytic anaemia than non-thalassaemic individuals.ConclusionsOur results provide information on the Jino ethnic minority that may be useful for further genetic counselling, prenatal screening and clinical diagnosis of thalassaemia in this region.
‘When something is this rare … how do you know bad really is bad…?’—views on prognostic discussions from patients with advanced soft tissue sarcoma
Authors: Gough Nicholas , Ross Joy R , Riley Julia , Judson Ian , Koffman Jonathan 
Published: December 2015

ObjectivesPrognostic disclosure among patients with cancer permits open informed discussion about treatment preferences and encourages advance care planning. In rare cancers such as soft tissue sarcoma, discussions regarding prognostication are challenging. Little is known about the consequences of this for patients or their preferences for such information. This qualitative study explores patient-centered accounts of the value and timing of prognostic discussions.Methods24 semistructured interviews were conducted with soft tissue sarcoma patients attending one London cancer centre: 66% female, median age 53 (range 19–82). The study was cross-sectional and participants were at different stages of the advanced disease trajectory. Interviews were digitally recorded, transcribed verbatim and analysed thematically using the framework approach.ResultsAll participants understood the incurable nature of advanced sarcoma. However, prognostic discussions were rare, always patient initiated and did not include known survival data, despite direct participant enquiry. Most participants did not wish to discuss prognosis at initial diagnosis but wished to be offered the opportunity to discuss this at intervals of disease progression, despite reservations it may not be helpful. Participants expected discussions to be clinician initiated. Three themes emerged to explain this position and included (1)Rarity causing prognostic uncertaintyreferring to patient belief that prognostication in rare cancers was less likely to be accurate than for common tumours; (2)Avoiding the negativesreferring to a wish not to hear unfavourable information and (3)Physical symptoms a better prognostic indicator than ‘physician guess’.ConclusionsAlthough 17/24 participants preferred not to discuss prognosis at initial diagnosis, they wished to have the opportunity to revisit prognostic discussions at intervals of disease progression. This may facilitate better advance care planning and end of life care.
Periodic oscillations of the forced Brusselator
Authors: Gallas J. A. C. 
Published: December 2015

We study the organization of stability phases in the control parameter space of a periodically driven Brusselator. Specifically, we report high-resolution stability diagrams classifying periodic phases in terms of the number of spikes per period of their regular oscillations. Such diagrams contain accumulations of periodic oscillations with an apparently unbounded growth in the number of their spikes. In addition to the entrainment horns, we investigate the organization of oscillations in the limit of small frequencies and amplitudes of the drive. We find this limit to be free from chaotic oscillations and to display an extended and regular tiling of periodic phases. The Brusselator contains also several features discovered recently in more complex scenarios like, e.g. in lasers and in biochemical reactions, and exhibits properties which are helpful in the generic classification of entrainment in driven systems. Our stability diagrams reveal snippets of how the full classification of oscillations might look like for a wide class of flows.
Association of High Ankle Brachial Index With Incident Cardiovascular Disease and Mortality in a High-Risk Population
Authors: Hendriks Eva J.E. , Westerink Jan , de Jong Pim A. , de Borst Gert J. , Nathoe Hendrik M. , Mali Willem P.Th.M. , van der Graaf Yolanda , van der Schouw Yvonne T. , Beulens Joline W. 
Published: December 2015

Objective—
The objective of this present study is to determine whether high ankle brachial index (ABI) as compared with ABIs within reference limits is associated with an increased incidence of cardiovascular disease (CVD) events and all-cause mortality in a high-risk population and whether this association is the same for patients with and without diabetes mellitus or prevalent CVD.

Approach and Results—
Seven thousand five hundred and thirty-eight patients with ABI>0.9 and either prevalent CVD or a high risk for CVD were selected from the Second Manifestations of Arterial Disease (SMART) study. Three hundred and thirty-six participants (4.5%) had high ABI (≥1.4 or incompressible). Higher age, male sex, higher body mass index, and diabetes mellitus were associated with higher prevalences of high ABI; smoking and higher non–high-density lipoprotein levels were associated with lower prevalences of high ABI. Cox proportional hazards models were fitted assessing the association of high ABI (as compared with ABI 0.9–1.4) with the risk of myocardial infarction, stroke, cardiovascular death, the combined outcome of these 3, and total mortality (median follow-up 6.9 years). After multivariable adjustment, high ABI was associated with an increased risk of myocardial infarction (hazard ratio 1.83 [95% confidence interval 1.22–2.76]), but not with stroke (hazard ratio 0.86 [95% confidence interval 0.44–1.69]), cardiovascular (hazard ratio 1.14 [95% confidence interval 0.70–1.84]), or all-cause mortality (hazard ratio 0.95 [95% confidence interval 0.67–1.34]). Associations of high ABI with CVD outcomes tended to be stronger in patients with diabetes mellitus but without statistically significant interactions.

Conclusions—
In a high-risk population, the presence of an ABI≥1.4 was associated with an increased risk for myocardial infarction, but not with stroke, all-cause, or vascular mortality.