bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metabolic Signatures of Bacterial Vaginosis
Authors: Srinivasan Sujatha , Morgan Martin T. , Fiedler Tina L. , Djukovic Danijel , Hoffman Noah G. , Raftery Daniel , Marrazzo Jeanne M. , Fredricks David N. 
Published: April 2015

ABSTRACT

Bacterial vaginosis (BV) is characterized by shifts in the vaginal microbiota from
Lactobacillus
dominant to a microbiota with diverse anaerobic bacteria. Few studies have linked specific metabolites with bacteria found in the human vagina. Here, we report dramatic differences in metabolite compositions and concentrations associated with BV using a global metabolomics approach. We further validated important metabolites using samples from a second cohort of women and a different platform to measure metabolites. In the primary study, we compared metabolite profiles in cervicovaginal lavage fluid from 40 women with BV and 20 women without BV. Vaginal bacterial representation was determined using broad-range PCR with pyrosequencing and concentrations of bacteria by quantitative PCR. We detected 279 named biochemicals; levels of 62% of metabolites were significantly different in women with BV. Unsupervised clustering of metabolites separated women with and without BV. Women with BV have metabolite profiles marked by lower concentrations of amino acids and dipeptides, concomitant with higher levels of amino acid catabolites and polyamines. Higher levels of the signaling eicosanoid 12-hydroxyeicosatetraenoic acid (12-HETE), a biomarker for inflammation, were noted in BV.
Lactobacillus crispatus
and
Lactobacillus jensenii
exhibited similar metabolite correlation patterns, which were distinct from correlation patterns exhibited by BV-associated bacteria. Several metabolites were significantly associated with clinical signs and symptoms (Amsel criteria) used to diagnose BV, and no metabolite was associated with all four clinical criteria. BV has strong metabolic signatures across multiple metabolic pathways, and these signatures are associated with the presence and concentrations of particular bacteria.

IMPORTANCE
Bacterial vaginosis (BV) is a common but highly enigmatic condition that is associated with adverse outcomes for women and their neonates. Small molecule metabolites in the vagina may influence host physiology, affect microbial community composition, and impact risk of adverse health outcomes, but few studies have comprehensively studied the metabolomics profile of BV. Here, we used mass spectrometry to link specific metabolites with particular bacteria detected in the human vagina by PCR. BV was associated with strong metabolic signatures across multiple pathways affecting amino acid, carbohydrate, and lipid metabolism, highlighting the profound metabolic changes in BV. These signatures were associated with the presence and concentrations of particular vaginal bacteria, including some bacteria yet to be cultivated, thereby providing clues as to the microbial origin of many metabolites. Insights from this study provide opportunities for developing new diagnostic markers of BV and novel approaches for treatment or prevention of BV.
Insights into Hydrocarbon Formation by Nitrogenase Cofactor Homologs
Authors: Lee Chi Chung , Hu Yilin , Ribbe Markus W. 
Published: April 2015

ABSTRACT

The L-cluster is an all-iron homolog of nitrogenase cofactors. Driven by europium(II) diethylenetriaminepentaacetate [Eu(II)-DTPA], the isolated L-cluster is capable of ATP-independent reduction of CO and CN
−
to C
1
to C
4
and C
1
to C
6
hydrocarbons, respectively. Compared to its cofactor homologs, the L-cluster generates considerably more CH
4
from the reduction of CO and CN
−
, which could be explained by the presence of a “free” Fe atom that is “unmasked” by homocitrate as an additional site for methanation. Moreover, the elevated CH
4
formation is accompanied by a decrease in the amount of longer hydrocarbons and/or the lengths of the hydrocarbon products, illustrating a competition between CH
4
formation/release and C−C coupling/chain extension. These observations suggest the possibility of designing simpler synthetic clusters for hydrocarbon formation while establishing the L-cluster as a platform for mechanistic investigations of CO and CN
−
reduction without complications originating from the heterometal and homocitrate components.

IMPORTANCE
Nitrogenase is a metalloenzyme that is highly complex in structure and uniquely versatile in function. It catalyzes two reactions that parallel two important industrial processes: the reduction of nitrogen to ammonia, which parallels the Haber-Bosch process in ammonia production, and the reduction of carbon monoxide to hydrocarbons, which parallels the Fischer-Tropsch process in fuel production. Thus, the significance of nitrogenase can be appreciated from the perspective of the useful products it generates: (i) ammonia, the “fixed” nitrogen that is essential for the existence of the entire human population; and (ii) hydrocarbons, the “recycled” carbon fuel that could be used to directly address the worldwide energy shortage. This article provides initial insights into the catalytic characteristics of various nitrogenase cofactors in hydrocarbon formation. The reported assay system provides a useful tool for mechanistic investigations of this reaction while suggesting the possibility of designing bioinspired catalysts based on nitrogenase cofactors.
Phylogenomic Analysis and Predicted Physiological Role of the Proton-Translocating NADH:Quinone Oxidoreductase (Complex I) Across Bacteria
Authors: Spero Melanie A. , Aylward Frank O. , Currie Cameron R. , Donohue Timothy J. 
Published: April 2015

ABSTRACTThe proton-translocating NADH:quinone oxidoreductase (complex I) is a multisubunit integral membrane enzyme found in the respiratory chains of both bacteria and eukaryotic organelles. Although much research has focused on the enzyme's central role in the mitochondrial respiratory chain, comparatively little is known about its role in the diverse energetic lifestyles of different bacteria. Here, we used a phylogenomic approach to better understand the distribution of complex I across bacteria, the evolution of this enzyme, and its potential roles in shaping the physiology of different bacterial groups. By surveying 970 representative bacterial genomes, we predict complex I to be present in ~50% of bacteria. While this includes bacteria with a wide range of energetic schemes, the presence of complex I is associated with specific lifestyles, including aerobic respiration and specific types of phototrophy (bacteria with only a type II reaction center). A phylogeny of bacterial complex I revealed five main clades of enzymes whose evolution is largely congruent with the evolution of the bacterial groups that encode complex I. A notable exception includes the gammaproteobacteria, whose members encode one of two distantly related complex I enzymes predicted to participate in different types of respiratory chains (aerobic versus anaerobic). Comparative genomic analyses suggest a broad role for complex I in reoxidizing NADH produced from various catabolic reactions, including the tricarboxylic acid (TCA) cycle and fatty acid beta-oxidation. Together, these findings suggest diverse roles for complex I across bacteria and highlight the importance of this enzyme in shaping diverse physiologies across the bacterial domain.IMPORTANCELiving systems use conserved energy currencies, including a proton motive force (PMF), NADH, and ATP. The respiratory chain enzyme, complex I, connects these energy currencies by using NADH produced during nutrient breakdown to generate a PMF, which is subsequently used for ATP synthesis. Our goal is to better understand the role of complex I in bacteria, whose energetic diversity allows us to view its function in a range of biological contexts. We analyzed sequenced bacterial genomes to predict the presence, evolution, and function of complex I in bacteria. We identified five main classes of bacterial complex I and predict that different classes participate in different types of respiratory chains (aerobic and anaerobic). We also predict that complex I helps maintain a cellular redox state by reoxidizing NADH produced from central metabolism. Our findings suggest diverse roles for complex I in bacterial physiology, highlighting the need for future laboratory-based studies.
Molecular Mechanism of Flocculation Self-Recognition in Yeast and Its Role in Mating and Survival
Authors: Goossens Katty V. Y. , Ielasi Francesco S. , Nookaew Intawat , Stals Ingeborg , Alonso-Sarduy Livan , Daenen Luk , Van Mulders Sebastiaan E. , Stassen Catherine , van Eijsden Rudy G. E. , Siewers Verena , Delvaux Freddy R. , Kasas Sandor , Nielsen Jens , Devreese Bart , Willaert Ronnie G. 
Published: April 2015

ABSTRACT

We studied the flocculation mechanism at the molecular level by determining the atomic structures of N-Flo1p and N-Lg-Flo1p in complex with their ligands. We show that they have similar ligand binding mechanisms but distinct carbohydrate specificities and affinities, which are determined by the compactness of the binding site. We characterized the glycans of Flo1p and their role in this binding process and demonstrate that glycan-glycan interactions significantly contribute to the cell-cell adhesion mechanism. Therefore, the extended flocculation mechanism is based on the self-interaction of Flo proteins and this interaction is established in two stages, involving both glycan-glycan and protein-glycan interactions. The crucial role of calcium in both types of interaction was demonstrated: Ca
2+
takes part in the binding of the carbohydrate to the protein, and the glycans aggregate only in the presence of Ca
2+
. These results unify the generally accepted lectin hypothesis with the historically first-proposed “Ca
2+
-bridge” hypothesis. Additionally, a new role of cell flocculation is demonstrated; i.e., flocculation is linked to cell conjugation and mating, and survival chances consequently increase significantly by spore formation and by introduction of genetic variability. The role of Flo1p in mating was demonstrated by showing that mating efficiency is increased when cells flocculate and by differential transcriptome analysis of flocculating versus nonflocculating cells in a low-shear environment (microgravity). The results show that a multicellular clump (floc) provides a uniquely organized multicellular ultrastructure that provides a suitable microenvironment to induce and perform cell conjugation and mating.

IMPORTANCE
Yeast cells can form multicellular clumps under adverse growth conditions that protect cells from harsh environmental stresses. The floc formation is based on the self-interaction of Flo proteins via an N-terminal PA14 lectin domain. We have focused on the flocculation mechanism and its role. We found that carbohydrate specificity and affinity are determined by the accessibility of the binding site of the Flo proteins where the external loops in the ligand-binding domains are involved in glycan recognition specificity. We demonstrated that, in addition to the Flo lectin-glycan interaction, glycan-glycan interactions also contribute significantly to cell-cell recognition and interaction. Additionally, we show that flocculation provides a uniquely organized multicellular ultrastructure that is suitable to induce and accomplish cell mating. Therefore, flocculation is an important mechanism to enhance long-term yeast survival.
Injury prevention strategies at the FIFA 2014 World Cup: perceptions and practices of the physicians from the 32 participating national teams
Authors: McCall Alan , Davison Michael , Andersen Thor Einar , Beasley Ian , Bizzini Mario , Dupont Gregory , Duffield Rob , Carling Chris , Dvorak Jiri 
Published: April 2015

PurposeThe available scientific research regarding injury prevention practices in international football is sparse. The purpose of this study was to quantify current practice with regard to (1) injury prevention of top-level footballers competing in an international tournament, and (2) determine the main challenges and issues faced by practitioners in these national teams.MethodsA survey was administered to physicians of the 32 competing national teams at the FIFA 2014 World Cup. The survey included 4 sections regarding perceptions and practices concerning non-contact injuries: (1) risk factors, (2) screening tests and monitoring tools, (3) preventative strategies and (4) reflection on their experience at the World Cup.ResultsFollowing responses from all teams (100%), the present study revealed the most important intrinsic (previous injury, accumulated fatigue, agonist:antagonist muscle imbalance) and extrinsic (reduced recovery time, training load prior to and during World Cup, congested fixtures) risk factors during the FIFA 2014 World Cup. The 5 most commonly used tests for risk factors were: flexibility, fitness, joint mobility, balance and strength; monitoring tools commonly used were: medical screen, minutes/matches played, subjective and objective wellness, heart rate and biochemical markers. The 5 most important preventative exercises were: flexibility, core, combined contractions, balance and eccentric.ConclusionsThe present study showed that many of the National football (soccer) teams’ injury prevention perceptions and practices follow a coherent approach. There remains, however, a lack of consistent research findings to support some of these perceptions and practices.
Usefulness of natriuretic peptide for the diagnosis of Kawasaki disease: a systematic review and meta-analysis
Authors: Lin Kuan-Ho , Chang Shy-Shin , Yu Chin-Wei , Lin Shen-Che , Liu Shu-Chun , Chao Hsiao-yun , Lee Meng-tse Gabriel , Wu Jiunn-Yih , Lee Chien-Chang 
Published: April 2015

ObjectiveTo examine the diagnostic value of serum B-type natriuretic peptide (BNP) in acute Kawasaki disease (KD).DesignSystematic review and meta-analysis.Data sourcesA systematic literature search strategy was designed and carried out using MEDLINE, EMBASE and the Cochrane Library from inception to December 2013. We also performed manual screening of the bibliographies of primary studies and review articles, and contacted authors for additional data.Study eligibility criteriaWe included all BNP and NT-pro (N-terminal prohormone) BNP assay studies that compared paediatric patients with KD to patients with febrile illness unrelated to KD. We excluded case reports, case series, review articles, editorials, congress abstracts, clinical guidelines and all studies that compared healthy controls.Primary and secondary outcome measuresThe performance characteristics of BNP were summarised using forest plots, hierarchical summary receiver operating characteristic (ROC) curves and bivariate random effects models.ResultsWe found six eligible studies including 279 cases of patients with KD and 203 febrile controls. Six studies examined NT-proBNP and one examined BNP. In general, NT-proBNP is a specific and moderately sensitive test for identifying KD. The pooled sensitivity was 0.89 (95% CI 0.78 to 0.95) and the pooled specificity was 0.72 (95% CI 0.58 to 0.82). The area under the summary ROC curve was 0.87 (95% CI 0.83 to 0.89). The positive likelihood ratio (LR+ 3.20, 95% CI 2.10 to 4.80) was sufficiently high to be qualified as a rule-in diagnostic tool in the context of high pre-test probability and compatible clinical symptoms. A high degree of heterogeneity was found using the Cochran Q statistic.ConclusionsCurrent evidence suggests that NT-proBNP may be used as a diagnostic tool for KD. NT-proBNP has high diagnostic value for identifying KD in patients with protracted undifferentiated febrile illness. Prospective large cohort studies are needed to help determine best cut-off values and further clarify the role of NT-proBNP in the diagnosis process of KD.
Use of the SONET score to evaluate Urgent Care Center overcrowding: a prospective pilot study
Authors: Wang Hao , Robinson Richard D , Cowden Chad D , Gorman Violet A , Cook Christopher D , Gicheru Eugene K , Schrader Chet D , Jayswal Rani D , Zenarosa Nestor R 
Published: April 2015

ObjectivesTo derive a tool to determine Urgent Care Center (UCC) crowding and investigate the association between different levels of UCC overcrowding and negative patient care outcomes.DesignProspective pilot study.SettingSingle centre study in the USA.Participants3565 patients who registered at UCC during the 21-day study period were included. Patients who had no overcrowding statuses estimated due to incomplete collection of operational variables at the time of registration were excluded in this study. 3139 patients were enrolled in the final data analysis.Primary and secondary outcome measuresA crowding estimation tool (SONET: Severely overcrowded, Overcrowded and Not overcrowded Estimation Tool) was derived using the linear regression analysis. The average length of stay (LOS) in UCC patients and the number of left without being seen (LWBS) patients were calculated and compared under the three different levels of UCC crowding.ResultsFour independent operational variables could affect the UCC overcrowding score including the total number of patients, the number of results pending for patients, the number of patients in the waiting room and the longest time a patient was stationed in the waiting room. In addition, UCC overcrowding was associated with longer average LOS (not overcrowded: 133±76 min, overcrowded: 169±79 min, and severely overcrowded: 196±87 min, p<0.001) and an increased number of LWBS patients (not overcrowded: 0.28±0.69 patients, overcrowded: 0.64±0.98, and severely overcrowded: 1.00±0.97).ConclusionsThe overcrowding estimation tool (SONET) derived in this study might be used to determine different levels of crowding in a high volume UCC setting. It also showed that UCC overcrowding might be associated with negative patient care outcomes.
Familial transmission of chronic obstructive pulmonary disease in adoptees: a Swedish nationwide family study
Authors: Zöller Bengt , Li Xinjun , Sundquist Jan , Sundquist Kristina 
Published: April 2015

ObjectivesFamilial clustering of chronic obstructive pulmonary disease (COPD) is well established, but the familial risk of COPD has not been determined among adoptees. The aim was to determine whether the familial transmission of COPD is related to disease in biological and/or adoptive parents.DesignHistoric cohort study.Participants80 214 (50% females).MethodsThe Swedish Multi-Generation Register was used to follow all Swedish-born adoptees born in 1932–2004 (n=80 214) between 1 January 1964 and 31 December 2010 for COPD (n=1978). The risk of COPD was estimated in adoptees with at least one biological parent with COPD but no adoptive parent with COPD (n=162) compared with adoptees without a biological or adoptive parent with COPD. The risk of COPD was also determined in adoptees with at least one adoptive parent but no biological parent with COPD (n=110), and in adoptees with both affected biological and adoptive parents (n=162).Primary outcome measureCOPD in adoptees.ResultsAdoptees with COPD in at least one biological parent but no adoptive parent were more likely to have COPD than adoptees without a biological or adoptive parent with COPD (standardised incidence ratio, SIR=1.98 (95% CI 1.69 to 2.31)). The familial SIR for adoptees with both a biological parent and an adoptive parent with COPD was 1.68 (95% CI 1.39 to 2.00). Adoptees with at least one adoptive parent with COPD but no biological parent with COPD were not at an increased risk of COPD (SIR=1.12 (95% CI 0.92 to 1.35)).ConclusionsThe findings of the study show that the familial transmission of COPD is associated with COPD in biological but not adoptive parents, suggesting that genetic or early life factors are important in the familial transmission of COPD.
001 KP: THE CURIOUS INCIDENT OF THE QUALITATIVE RESEARCHER IN APPLIED HEALTH RESEARCH
Authors: Shaw S 
Published: April 2015

Qualitative research is widely used as a means of understanding and analysing a range of health and care issues. Qualitative researchers are a diverse group who use interpretive approaches to make the world visible (for instance, through case study, interviewing or participant observation). This makes them well-placed to study health care and to apply findings in practice and yet few describe themselves as doing ‘applied health research’. This raises the question as to whether applied qualitative health research is alive and kicking or whether, like the dog in the opening paragraph of Mark Haddon's booka, it's lying on its side with its eyes closed and seemingly dead? In seeking to answer that question, this paper focuses on current challenges facing qualitative researchers working in applied settings.There is a vibrant community of qualitative researchers who are doing applied health research and who aspire to make a difference to people's lives. High quality research is being undertaken that should not only make a difference but also raise the profile of qualitative health research. However, involvement in applied health research often involves compromises about the ways in which we work. It tends to involve multidisciplinary teams working together for short periods of time on specific problems in the real world, and it often requires researchers to work across disciplines and teams, proactively manage relationships, combine research methodologies and reconsider theoretical or epistemological concerns. Those working in applied health research need to take care not to give up some of the important elements of qualitative research to the methodological hierarchy that mixed-methods designs sometimes presume in which quantitative methods are at the top and qualitative methods are relegated to a largely auxiliary role. They must ensure that methodological and disciplinary differences are confronted and addressed, rather than one subsuming or dominating the other. And they must ensure that theoretically-oriented work features strongly in applied health research: infusing research design, underpinning methodology and informing how data are analysed and interpreted.Considerable progress has already been made in each of these areas. However, more could be done to ensure that when we do qualitative research we do it to the highest quality and are then confident in the value of our work. In doing so, we can then ensure that applied research is alive and kicking and with us for a long time to come.aThe Curious Incident of the Dog in the Night-Time, written by Mark Haddon and published by Vintage in 2004.