bluuebunny/crossref_metadata_2025_split huggingface dataset:
Options and Limitations in Clinical Investigation of Bacterial Biofilms
Authors: Magana Maria , Sereti Christina , Ioannidis Anastasios , Mitchell Courtney A. , Ball Anthony R. , Magiorkinis Emmanouil , Chatzipanagiotou Stylianos , Hamblin Michael R. , Hadjifrangiskou Maria , Tegos George P. 
Published: April 2018

SUMMARYBacteria can form single- and multispecies biofilms exhibiting diverse features based upon the microbial composition of their community and microenvironment. The study of bacterial biofilm development has received great interest in the past 20 years and is motivated by the elegant complexity characteristic of these multicellular communities and their role in infectious diseases. Biofilms can thrive on virtually any surface and can be beneficial or detrimental based upon the community's interplay and the surface. Advances in the understanding of structural and functional variations and the roles that biofilms play in disease and host-pathogen interactions have been addressed through comprehensive literature searches. In this review article, a synopsis of the methodological landscape of biofilm analysis is provided, including an evaluation of the current trends in methodological research. We deem this worthwhile because a keyword-oriented bibliographical search reveals that less than 5% of the biofilm literature is devoted to methodology. In this report, we (i) summarize current methodologies for biofilm characterization, monitoring, and quantification; (ii) discuss advances in the discovery of effective imaging and sensing tools and modalities; (iii) provide an overview of tailored animal models that assess features of biofilm infections; and (iv) make recommendations defining the most appropriate methodological tools for clinical settings.
Comparison of Immunogenicity and Protection of Two Pneumococcal Protein Vaccines Based on PsaA and PspA
Authors: Yu Jinfei , Li Bo , Chen Xiaorui , Lu Jingcai , Wang Dandan , Gu Tiejun , Kong Wei , Wu Yongge 
Published: April 2018

ABSTRACT

Streptococcus pneumoniae
is a major cause of invasive pneumococcal disease, septicemia, and meningitis that can result in high morbidity rates in children under 5 years old. The current polysaccharide-based vaccines can provide type-specific immunity, but a broad-spectrum vaccine would provide greater coverage. Therefore, developing pneumococcal-protein-based vaccines that can extend to more serum types is highly important. In this study, we vaccinated mice via the subcutaneous (s.c.) route with a systemic vaccine that is a mixture of fusion protein PsaA-PspA23 and a single protein, PspA4, with aluminum hydroxide as an adjuvant. As a comparison, mice were immunized intranasally with a mucosal vaccine that is a mixture of PspA2-PA-BLP (where PA is protein anchor and BLP is bacterium-like particle) and PspA4-PA-BLP, via the intranasal (i.n.) route. The two immunization processes were followed by challenge with
Streptococcus pneumoniae
bacteria from two different PspA families. Specific IgG titers in the serum and specific IgA titers in the mucosa were determined following immunizations. Bacterial loads and survival rates after challenge were compared. Both the systemic vaccine and the mucosal vaccine induced a significant increase of IgG against PspAs. Only the mucosal vaccine also induced specific IgA in the mucosa. The two vaccines provided protection, but each vaccine showed an advantage. The systemic vaccine induced higher levels of serum antibodies, whereas the mucosal vaccine limited the bacterial load in the lung and blood. Therefore, coimmunizations with the two types of vaccines may be implemented in the future.
Two-Component Flavin-Dependent Riboflavin Monooxygenase Degrades Riboflavin in Devosia riboflavina
Authors: Kanazawa Hiroshi , Shigemoto Ryosuke , Kawasaki Yukie , Oinuma Ken-Ichi , Nakamura Akira , Masuo Shunsuke , Takaya Naoki 
Published: April 2018

ABSTRACT

The actinobacterium
Microbacterium maritypicum
splits riboflavin (vitamin B
2
) into lumichrome and
d
-ribose. However, such degradation by other bacteria and the involvement of a two-component flavin-dependent monooxygenase (FMO) in the reaction remain unknown. Here we investigated the mechanism of riboflavin degradation by the riboflavin-assimilating alphaproteobacterium
Devosia riboflavina
(formerly
Pseudomonas riboflavina
). We found that adding riboflavin to bacterial cultures induced riboflavin-degrading activity and a protein of the FMO family that had 67% amino acid identity with the predicted riboflavin hydrolase (RcaE) of
M. maritypicum
MF109. The
D. riboflavina
genome clustered genes encoding the predicted FMO, flavin reductase (FR), ribokinase, and flavokinase, and riboflavin induced their expression. This finding suggests that these genes constitute a mechanism for utilizing riboflavin as a carbon source. Recombinant FMO (rFMO) protein of
D. riboflavina
oxidized riboflavin in the presence of reduced flavin mononucleotide (FMN) provided by recombinant FR (rFR), oxidized FMN and NADH, and produced stoichiometric amounts of lumichrome and
d
-ribose. Further investigation of the enzymatic properties of
D. riboflavina
rFMO indicated that rFMO-rFR coupling accompanied O
2
consumption and the generation of enzyme-bound hydroperoxy-FMN, which are characteristic of two-component FMOs. These results suggest that
D. riboflavina
FMO is involved in hydroperoxy-FMN-dependent mechanisms to oxygenize riboflavin and a riboflavin monooxygenase is necessary for the initial step of riboflavin degradation.

IMPORTANCE
Whether bacteria utilize either a monooxygenase or a hydrolase for riboflavin degradation has remained obscure. The present study found that a novel riboflavin monooxygenase, not riboflavin hydrolase, facilitated this process in
D. riboflavina
. The riboflavin monooxygenase gene was clustered with flavin reductase, flavokinase, and ribokinase genes, and riboflavin induced their expression and riboflavin-degrading activity. The gene cluster is uniquely distributed in
Devosia
species and actinobacteria, which have exploited an environmental niche by developing adaptive mechanisms for riboflavin utilization.
Defining and Evaluating a Core Genome Multilocus Sequence Typing Scheme for Genome-Wide Typing of Clostridium difficile
Authors: Bletz Stefan , Janezic Sandra , Harmsen Dag , Rupnik Maja , Mellmann Alexander 
Published: April 2018

ABSTRACT

Clostridium difficile
, recently renamed
Clostridioides difficile
, is the most common cause of antibiotic-associated nosocomial gastrointestinal infections worldwide. To differentiate endogenous infections and transmission events, highly discriminatory subtyping is necessary. Today, methods based on whole-genome sequencing data are increasingly used to subtype bacterial pathogens; however, frequently a standardized methodology and typing nomenclature are missing. Here we report a core genome multilocus sequence typing (cgMLST) approach developed for
C. difficile
. Initially, we determined the breadth of the
C. difficile
population based on all available MLST sequence types with Bayesian inference (BAPS). The resulting BAPS partitions were used in combination with
C. difficile
clade information to select representative isolates that were subsequently used to define cgMLST target genes. Finally, we evaluated the novel cgMLST scheme with genomes from 3,025 isolates. BAPS grouping (
n
= 6 groups) together with the clade information led to a total of 11 representative isolates that were included for cgMLST definition and resulted in 2,270 cgMLST genes that were present in all isolates. Overall, 2,184 to 2,268 cgMLST targets were detected in the genome sequences of 70 outbreak-associated and reference strains, and on average 99.3% cgMLST targets (1,116 to 2,270 targets) were present in 2,954 genomes downloaded from the NCBI database, underlining the representativeness of the cgMLST scheme. Moreover, reanalyzing different cluster scenarios with cgMLST were concordant to published single nucleotide variant analyses. In conclusion, the novel cgMLST is representative for the whole
C. difficile
population, is highly discriminatory in outbreak situations, and provides a unique nomenclature facilitating interlaboratory exchange.
Brain Large Artery Lymphocytic Inflammation and Human Immunodeficiency Virus-Related Brain Arterial Remodeling
Authors: Shenoy Adele , Dwork Andrew , Elkind Mitchell S. V. , Marshall Randolph , Morgello Susan , Gutierrez Jose 
Published: April 2018

ABSTRACT

The pathogenesis of increased stroke risk in human immunodeficiency virus (HIV) remains unclear. Our study investigated the relationship between adventitial and intimal CD3
+
T cells and brain arterial remodeling that potentially contributes to HIV-related vasculopathy and stroke. Large brain arteries from 84 HIV
+
cases and 78 HIV
−
cases were analyzed to determine interadventitial and luminal diameters, intimal and wall thickness, percent stenosis, and the presence of atherosclerosis. Immunohistochemical analysis was performed to detect and visually score CD3, a pan-T-cell marker, in the intima and adventitia. Our study showed that numbers of adventitial CD3
+
T cells are lower among persons with HIV than among those without HIV, especially if CD4 counts are <200, though intimal CD3
+
T cell numbers did not differ by HIV status. Among those with HIV but CD4 counts of <200 at the time of death, intimal CD3
+
T cells were associated with hypertrophic outward remodeling, while among those with HIV and CD4 of >200 or HIV
−
controls, intimal CD3
+
T cells were associated with hypertrophic inward remodeling. We conclude that intimal lymphocytic inflammation is involved in brain arterial remodeling that may contribute to HIV-related cerebrovascular pathology.

IMPORTANCE
Although mortality from human immunodeficiency virus (HIV) has decreased with the use of combination antiretroviral therapies, there is now an increased risk of cardiovascular and cerebrovascular disease associated with HIV. Thus, there is a need to understand the pathogenesis of stroke in HIV infection. Our study examines how lymphocytic inflammation in brain arteries may contribute to increased cerebral vasculopathy. With this understanding, our study can potentially help direct future therapies to target and prevent brain arterial remodeling processes associated with HIV.
Frequency–risk relationships between second-hand smoke exposure and respiratory symptoms among adolescents: a cross-sectional study in South China
Authors: Chen Zhiyao , Liu Guocong , Chen Jianying , Li Shunming , Jiang Ting , Xu Bin , Ye Xiaohua 
Published: April 2018

ObjectivesAlthough previous studies have suggested an association between second-hand smoke (SHS) exposure and respiratory symptoms, current evidence is inconsistent. Additionally, it remains unclear whether there are frequency–risk relationships between SHS exposure and respiratory symptoms among adolescents.MethodsA cross-sectional survey was conducted using a stratified cluster sampling method to obtain a representative sample of high school students in Guangzhou, China. The respiratory symptoms were defined as persistent cough or sputum for three consecutive months during the past 12 months. Self-reported SHS exposure was defined as non-smokers' inhalation of the smoke exhaled from smokers on ≥1 day a week in the past 7 days. The univariable and multivariable logistic regression models were fitted to explore the potential frequency–risk relationships between SHS exposure and respiratory symptoms.ResultsAmong 3575 students, the overall prevalence of SHS exposure was 69.2%, including 49.5% for SHS in public places, 34.5% in homes, 22.7% in indoor campuses and 29.2% in outdoor campuses. There were significantly increased risks of having respiratory symptoms corresponding to SHS exposure in public places (OR=1.60, 95% CI 1.30 to 1.95), in homes (OR=1.53, 95% CI 1.25 to 1.87), in indoor campuses (OR=1.43, 95% CI 1.14 to 1.79) and in outdoor campuses (OR=1.37, 95% CI 1.10 to 1.69) using no exposure as reference. Notably, we observed monotonic frequency–risk relationships between setting-specific(eg, homes, public places and campuses) SHS exposure and respiratory symptoms.ConclusionOur findings suggest that setting-specific SHS exposure is associated with a significant, dose-dependent increase in risk of respiratory symptoms.
Comparison of prognostic models to predict the occurrence of colorectal cancer in asymptomatic individuals: a systematic literature review and external validation in the EPIC and UK Biobank prospective cohort studies
Authors: Smith Todd , Muller David C , Moons Karel G M , Cross Amanda J , Johansson Mattias , Ferrari Pietro , Fagherazzi Guy , Peeters Petra H M , Severi Gianluca , Hüsing Anika , Kaaks Rudolf , Tjonneland Anne , Olsen Anja , Overvad Kim , Bonet Catalina , Rodriguez-Barranco Miguel , Huerta Jose Maria , Barricarte Gurrea Aurelio , Bradbury Kathryn E , Trichopoulou Antonia , Bamia Christina , Orfanos Philippos , Palli Domenico , Pala Valeria , Vineis Paolo , Bueno-de-Mesquita Bas , Ohlsson Bodil , Harlid Sophia , Van Guelpen Bethany , Skeie Guri , Weiderpass Elisabete , Jenab Mazda , Murphy Neil , Riboli Elio , Gunter Marc J , Aleksandrova Krasimira Jekova , Tzoulaki Ioanna 
Published: April 2018

ObjectiveTo systematically identify and validate published colorectal cancer risk prediction models that do not require invasive testing in two large population-based prospective cohorts.DesignModels were identified through an update of a published systematic review and validated in the European Prospective Investigation into Cancer and Nutrition (EPIC) and the UK Biobank. The performance of the models to predict the occurrence of colorectal cancer within 5 or 10 years after study enrolment was assessed by discrimination (C-statistic) and calibration (plots of observed vs predicted probability).ResultsThe systematic review and its update identified 16 models from 8 publications (8 colorectal, 5 colon and 3 rectal). The number of participants included in each model validation ranged from 41 587 to 396 515, and the number of cases ranged from 115 to 1781. Eligible and ineligible participants across the models were largely comparable. Calibration of the models, where assessable, was very good and further improved by recalibration. The C-statistics of the models were largely similar between validation cohorts with the highest values achieved being 0.70 (95% CI 0.68 to 0.72) in the UK Biobank and 0.71 (95% CI 0.67 to 0.74) in EPIC.ConclusionSeveral of these non-invasive models exhibited good calibration and discrimination within both external validation populations and are therefore potentially suitable candidates for the facilitation of risk stratification in population-based colorectal screening programmes. Future work should both evaluate this potential, through modelling and impact studies, and ascertain if further enhancement in their performance can be obtained.
Genomic retained heterosis effects on fertility and lifetime productivity in beef heifers
Authors: Basarab J.A. , Crowley J.J. , Abo-Ismail M.K. , Manafiazar G.M. , Akanno E.C. , Baron V.S. , Plastow G. 
Published: April 2018

This study evaluated the effects of three genomic indicators of heterosis on female fertility and lifetime productivity, and quantified changes over 11 production cycles in a crossbred cow herd. Pedigree-based breed composition (pBC) was determined and used to calculate retained heterozygosity for 412 replacement heifers born from 2004 to 2014 at the Lacombe Research and Development Centre (AB, Canada). Heifers were followed as cows over 1050 mating opportunities, 11 production cycles, and five parities. Heifers and their sires (51) were genotyped and these genotypes were used to predict each animal’s genomic breed composition (gBC) and three genomic indicators of heterosis: (1) retained heterozygosity (RHETg), (2) heterozygous proportion (H), and (3) retained heterosis (RHg). Correlations between pedigree and genomic breed fractions for Angus, Hereford, and Charolais were high (rp = 0.74–0.94; P < 0.001). Genomic indicators of heterosis were highly related (rp = 0.61 for RHETg vs. H; 0.71 for RHg vs. H; 0.96 for RHETg vs. RHg; P < 0.001). Each 10% change in RHETg resulted in 51 ± 20 d longer survival (P = 0.011) in the herd and 35.7 ± 15.2 kg more (P = 0.019) calf wean weight per cow exposed to breeding when summed over five parities. These differences resulted in an extra $161 per heifer in a year. Optimizing heterosis using genomic tools can be very beneficial for the cow herd if applied correctly.
IL21 Therapy Combined with PD-1 and Tim-3 Blockade Provides Enhanced NK Cell Antitumor Activity against MHC Class I–Deficient Tumors
Authors: Seo Hyungseok , Kim Byung-Seok , Bae Eun-Ah , Min Byung Soh , Han Yoon Dae , Shin Sang Joon , Kang Chang-Yuil 
Published: April 2018

Abstract
Increased expression of coinhibitory molecules such as PD-1 and Tim-3 on NK cells has been demonstrated in advanced cancer patients who harbor MHC class I–deficient tumors. However, even in preclinical models, the antitumor effects of checkpoint blockade on NK cells have not been clearly elucidated. Here, we show that anti–PD-1/anti–Tim-3 treatment suppressed tumor progression in mice bearing MHC class I–deficient tumors, and the suppression was further enhanced by recombinant IL21 (rIL21) treatments through an NK-cell–dependent mechanism. We also show that the intratumoral delivery of rIL21 attracted NK cells to the tumor site in a CXCR3-dependent fashion. A combination of IL21 and checkpoint blockade facilitated the effector function of exhausted NK cells in cancer patients. Given the effects of the checkpoint blockade and rIL21 combination on NK cells infiltrating into MHC class I–deficient tumors, we suggest that the efficacy of checkpoint blockade can be enhanced through the administration of IL21 for advanced cancer patients with MHC class I–low/deficient tumors. Cancer Immunol Res; 6(6); 685–95. ©2018 AACR.
Nutritional evaluation of millet at different seeding rates and cutting heights
Authors: Milke Lilian Monise , Campana Mariana , Antônio Giovani , Morais Jozivaldo Prudêncio Gomes de , Zilio Elissandra Maiara de Castro , Santos Juliana Aparecida Alves dos , Del Valle Tiago Antonio 
Published: April 2018

This study evaluated the effect of different seeding rates and cutting heights on production and composition of millet. Two randomized block design experiments were performed. In the first trial, 32 parcels (1.2 × 1.2 m) were used for evaluation of seeding rate of 24, 35, 50 and 60 kg/ha. Three cuts were carried out to evaluate plant height, fresh and dry mass yield, dry matter (DM), neutral detergent fiber (NDF), crude protein (CP) and acid detergent lignin (ADL) concentration and in situ DM and NDF digestibility. In the second trial, 20 parcels (1.2 × 3.0 m) were used to evaluate 20, 30, 40 and 50 cm of cutting heights for two growing cycles, performing the evaluations previously listed. Seeding rate linearly increased plant height, fresh and dry mass production, and tended to linearly decrease dry matter in situ digestibility, without effects on forage composition. Cutting height had no effect on crude protein (CP) concentration, but linearly increased plant height, dry mass production, DM content and tended to decrease NDF in situ digestibility and ADL content. Thus, the use of the highest evaluated seeding rates (60 kg/ha) and cutting height (50 cm) increased forage production; however, the use of the lowest residual height increased forage quality.
Association of Biomarker Clusters With Cardiac Phenotypes and Mortality in Patients With HIV Infection
Authors: Scherzer Rebecca , Shah Sanjiv J. , Secemsky Eric , Butler Javed , Grunfeld Carl , Shlipak Michael G. , Hsue Priscilla Y. 
Published: April 2018

Background:
Although individual cardiac biomarkers are associated with heart failure risk and all-cause mortality in HIV-infected individuals, their combined use for prediction has not been well studied.

Methods and Results:
Unsupervised k-means cluster analysis was performed blinded to the study outcomes in 332 HIV-infected participants on 8 biomarkers: ST2, NT-proBNP (N-terminal pro-B-type natriuretic peptide), hsCRP (high-sensitivity C-reactive protein), GDF-15 (growth differentiation factor 15), cystatin C, IL-6 (interleukin-6), D-dimer, and troponin. We evaluated cross-sectional associations of each cluster with diastolic dysfunction, pulmonary hypertension (defined as echocardiographic pulmonary artery systolic pressure ≥35 mm Hg), and longitudinal associations with all-cause mortality. The biomarker-derived clusters partitioned subjects into 3 groups. Cluster 3 (n=103) had higher levels of CRP, IL-6, and D-dimer (inflammatory phenotype). Cluster 2 (n=86) displayed elevated levels of ST2, NT-proBNP, and GDF-15 (cardiac phenotype). Cluster 1 (n=143) had lower levels of both phenotype-associated biomarkers. After multivariable adjustment for traditional and HIV-related risk factors, cluster 3 was associated with a 51% increased risk of diastolic dysfunction (95% confidence interval, 1.12–2.02), and cluster 2 was associated with a 67% increased risk of pulmonary hypertension (95% confidence interval, 1.04–2.68), relative to cluster 1. Over a median 6.9-year follow-up, 48 deaths occurred. Cluster 3 was independently associated with a 3.3-fold higher risk of mortality relative to cluster 1 (95% confidence interval, 1.3–8.1), and cluster 2 had a 3.1-fold increased risk (95% confidence interval, 1.1–8.4), even after controlling for diastolic dysfunction, pulmonary hypertension, left ventricular mass, and ejection fraction.

Conclusions:
Serum biomarkers can be used to classify HIV-infected individuals into separate clusters for differentiating cardiopulmonary structural and functional abnormalities and can predict mortality independent of these structural and functional measures.
DNA barcoding, phylogeny and phylogeography of the cyst nematode species of the Avenae group from the genus Heterodera (Tylenchida: Heteroderidae)
Authors: Subbotin Sergei A. , Toumi Fateh , Elekçioğlu Ibrahim Halil , Waeyenberge Lieven , Tanha Maafi Zahra 
Published: April 2018

Summary
Among the recognised species groups of Heterodera, the Avenae group is one of the largest with a total of 12 species. Ten of them, H. arenaria, H. aucklandica, H. australis, H. avenae, H. filipjevi, H. mani, H. pratensis, H. riparia, H. sturhani and H. ustinovi, are morphologically closely related and represent the H. avenae species complex, and the other two, H. hordecalis and H. latipons, are morphologically more distinct from this complex. In this study we provide comprehensive phylogenetic analyses of several hundred COI and ITS rRNA gene sequences from the Avenae group using Bayesian inference, maximum likelihood and statistical parsimony. Some 220 COI and 11 ITS rRNA new gene sequences from 147 nematode populations collected in 26 countries were obtained in this study. Our study showed that the COI gene is a powerful DNA barcoding marker for identification of populations and species from the Avenae group. A putatively new cyst nematode species related to H. latipons was revealed from the analysis of COI and ITS rRNA gene datasets. COI gene sequences allow distinguishing H. arenaria, H. australis and H. sturhani from each other and other species. Problems of species delimiting of these species are discussed. The results of the analysis showed that COI haplotypes corresponded to certain pathotypes of the cereal cyst nematodes. It is recommended that information on COI haplotypes of studied populations be included in research with these nematodes. Based on the results of phylogeographical analysis and age estimation of clades with a molecular clock approach, it was hypothesised that several species of the Avenae group primarily originated and diversified in the Irano-Anatolian hotspot during the Pleistocene and Holocene periods and then dispersed from this region across the world. Different geographic barriers, centres and times of origin might explain current known distribution patterns for species of the Avenae group. Possible pathways, including a long distance trans-Atlantic dispersal, and secondary centres of diversification are proposed and discussed.