bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patterns of diversification in a North American endemic fish, the Blackbanded Darter (Perciformes, Percidae)
Authors: Hayes Malorie M. , Piller Kyle R. 
Published: May 2018

The coastal plain of the south‐eastern United States shows multiple biogeographic patterns of plant and animal dispersal; however, few freshwater fish taxa span these biogeographic barriers. Percina nigrofasciata, the Blackbanded Darter (Teleostomi: Percidae), is a small, benthic, freshwater fish species with an extensive range in the south‐eastern United States. Recently, two species have been elevated from within P. nigrofasciata: P. crypta and P. westfalli, but their ranges have not been established. We broadly sampled across the south‐eastern United States, encompassing the range of P. nigrofasciata sensu lato. We reconstruct the phylogeny of Percina using both mitochondrial and nuclear markers. Eighty‐four specimens of Percina nigrofasciata were sampled for the mitochondrial gene cytochrome b (1,119 bp) to form a base phylogeny. The nuclear marker S7‐I1 was subsampled across populations to detect instances of hybridization. Phylogenetic relationships with other members of the genus Percina were assessed through Bayesian inference. Our results suggest that Percina nigrofasciata sensu stricto occurs from the Lake Pontchartrain Basin in Louisiana to the rivers of the Mobile Basin with little genetic structuring throughout its range. Percina westfalli occurs from the Apalachicola River drainages to the Atlantic Slope from the Savannah River to the St. Johns River. We find that P. crypta is not genetically distinct from P. westfalli in the Chattahoochee and Flint Rivers. Possible ancestral hybridization occurred between the P. nigrofasciata and P. westfalli in the panhandle of Florida between Mobile Bay and the Apalachicola River.
Body size downgrading of mammals over the late Quaternary
Authors: Smith Felisa A. , Elliott Smith Rosemary E. , Lyons S. Kathleen , Payne Jonathan L. 
Published: May 2018

Megafaunal lossToday, it is well known that human activities put larger animals at greater risk of extinction. Such targeting of the largest species is not new, however. Smithet al.show that biased loss of large-bodied mammal species from ecosystems is a signature of human impacts that has been following hominin migrations since the Pleistocene. If the current trend continues, terrestrial mammal body sizes will become smaller than they have been over the past 45 million years. Megafaunal mammals have a major impact on the structure of ecosystems, so their loss could be particularly damaging.Science, this issue p.310
Impact of Bacterial Membrane Fatty Acid Composition on the Failure of Daptomycin To Kill Staphylococcus aureus
Authors: Boudjemaa Rym , Cabriel Clément , Dubois-Brissonnet Florence , Bourg Nicolas , Dupuis Guillaume , Gruss Alexandra , Lévêque-Fort Sandrine , Briandet Romain , Fontaine-Aupart Marie-Pierre , Steenkeste Karine 
Published: May 2018

ABSTRACT

Daptomycin is a last-resort membrane-targeting lipopeptide approved for the treatment of drug-resistant staphylococcal infections, such as bacteremia and implant-related infections. Although cases of resistance to this antibiotic are rare, increasing numbers of clinical,
in vitro
, and animal studies report treatment failure, notably against
Staphylococcus aureus
. The aim of this study was to identify the features of daptomycin and its target bacteria that lead to daptomycin treatment failure. We show that daptomycin bactericidal activity against
S. aureus
varies significantly with the growth state and strain, according to the membrane fatty acid composition. Daptomycin efficacy as an antibiotic relies on its ability to oligomerize within membranes and form pores that subsequently lead to cell death. Our findings ascertain that daptomycin interacts with tolerant bacteria and reaches its membrane target, regardless of its bactericidal activity. However, the final step of pore formation does not occur in cells that are daptomycin tolerant, strongly suggesting that it is incapable of oligomerization. Importantly, membrane fatty acid contents correlated with poor daptomycin bactericidal activity, which could be manipulated by fatty acid addition. In conclusion, daptomycin failure to treat
S. aureus
is not due to a lack of antibiotic-target interaction, but is driven by its capacity to form pores, which depends on membrane composition. Manipulation of membrane fluidity to restore
S. aureus
daptomycin bactericidal activity
in vivo
could open the way to novel antibiotic treatment strategies.
Population Pharmacokinetic Model and Meta-analysis of Outcomes of Amphotericin B Deoxycholate Use in Adults with Cryptococcal Meningitis
Authors: Stott Katharine E. , Beardsley Justin , Whalley Sarah , Kibengo Freddie Mukasa , Mai Nguyen Thi Hoang , Tùng Nguyễn Lê Nhu' , Cuc Ngo Thi Kim , Kolamunnage-Dona Ruwanthi , Hope William , Day Jeremy 
Published: May 2018

ABSTRACTThere is a limited understanding of the population pharmacokinetics (PK) and pharmacodynamics (PD) of amphotericin B deoxycholate (DAmB) for cryptococcal meningitis. A PK study was conducted inn= 42 patients receiving DAmB (1 mg/kg of body weight every 24 h [q24h]). A 2-compartment PK model was developed. Patient weight influenced clearance and volume in the final structural model. Monte Carlo simulations estimated drug exposure associated with various DAmB dosages. A search was conducted for trials reporting outcomes of treatment of cryptococcal meningitis patients with DAmB monotherapy, and a meta-analysis was performed. The PK parameter means (standard deviations) were as follows: clearance, 0.03 (0.01) × weight + 0.67 (0.01) liters/h; volume, 0.82 (0.80) × weight + 1.76 (1.29) liters; first-order rate constant from central compartment to peripheral compartment, 5.36 (6.67) h−1; first-order rate constant from peripheral compartment to central compartment, 9.92 (12.27) h−1. The meta-analysis suggested that the DAmB dosage explained most of the heterogeneity in cerebrospinal fluid (CSF) sterility outcomes but not in mortality outcomes. Simulations of values corresponding to the area under concentration-time curve from h 144 to h 168 (AUC144–168) resulted in median (interquartile range) values of 5.83 mg · h/liter (4.66 to 8.55), 10.16 mg · h/liter (8.07 to 14.55), and 14.51 mg · h/liter (11.48 to 20.42) with dosages of 0.4, 0.7, and 1.0 mg/kg q24h, respectively. DAmB PK is described adequately by a linear model that incorporates weight with clearance and volume. Interpatient PK variability is modest and unlikely to be responsible for variability in clinical outcomes. There is discordance between the impact that drug exposure has on CSF sterility and its impact on mortality outcomes, which may be due to cerebral pathology not reflected in CSF fungal burden, in addition to clinical variables.
Molecular Characterization of Invasive Isolates of Neisseria meningitidis in Casablanca, Morocco
Authors: Razki Aziza , Hong Eva , Zerouali Khalid , Belabbes Houria , Aitmouss Khadija , Terrade Aude , Zaki Bahija , Deghmane Ala-Eddine , Elmdaghri Naima , Taha Muhamed-Kheir 
Published: May 2018

ABSTRACT

Meningococcal epidemiology may change unpredictably, and typing of
Neisseria meningitidis
isolates is crucial for the surveillance of invasive meningococcal disease (IMD). Few data are available regarding the meningococcal epidemiology in countries of North Africa. We aimed to explore invasive meningococcal isolates from the Casablanca region in Morocco. We used whole-genome sequencing (WGS) to characterize 105 isolates from this region during the period of 2011 to 2016. Our data showed that the majority (
n
= 100) of the isolates belonged to serogroup B. Genotyping indicated that most of the isolates (
n
= 62) belonged to sequence type 33 of clonal complex 32. The isolates also showed the same PorA and FetA markers and clustered together on the basis of WGS phylogenetic analysis; they seemed to correspond to an expansion of local isolates in the Casablanca region, as reported for similar isolates in several other countries. These data suggest that serogroup B isolates may predominate in Morocco, which may have an important impact in the design of vaccination strategies.
Identification of the Intragenomic Promoter Controlling Hepatitis E Virus Subgenomic RNA Transcription
Authors: Ding Qiang , Nimgaonkar Ila , Archer Nicholas F. , Bram Yaron , Heller Brigitte , Schwartz Robert E. , Ploss Alexander 
Published: May 2018

ABSTRACT

Approximately 20 million hepatitis E virus (HEV) infections occur annually in both developing and industrialized countries. Most infections are self-limiting, but they can lead to chronic infections and cirrhosis in immunocompromised patients, and death in pregnant women. The mechanisms of HEV replication remain incompletely understood due to scarcity of adequate experimental platforms. HEV undergoes asymmetric genome replication, but it produces an additional subgenomic (SG) RNA encoding the viral capsid and a viroporin in partially overlapping open reading frames. Using a novel transcomplementation system, we mapped the intragenomic subgenomic promoter regulating SG RNA synthesis. This
cis
-acting element is highly conserved across all eight HEV genotypes, and when the element is mutated, it abrogates particle assembly and release. Our work defines previously unappreciated viral regulatory elements and provides the first in-depth view of the intracellular genome dynamics of this emerging human pathogen.

IMPORTANCE
HEV is an emerging pathogen causing severe liver disease. The genetic information of HEV is encoded in RNA. The genomic RNA is initially copied into a complementary, antigenomic RNA that is a template for synthesis of more genomic RNA and for so-called subgenomic RNA. In this study, we identified the precise region within the HEV genome at which the synthesis of the subgenomic RNA is initiated. The nucleotides within this region are conserved across genetically distinct variants of HEV, highlighting the general importance of this segment for the virus. To identify this regulatory element, we developed a new experimental system that is a powerful tool with broad utility to mechanistically dissect many other poorly understood functional elements of HEV.
Comparison of long-term clinical evolution in highly myopic eyes with vertical oval-shaped dome with or without untreated serous retinal detachment
Authors: García-Ben Antonio , Garcia-Basterra Ignacio , González-Gómez Ana , Baquero-Aranda Isabel , Morillo-Sanchez María José , Soler-García Antonio , García-Campos Jose Manuel 
Published: May 2018

Background
To compare the long-term clinical evolution of highly myopic eyes with vertical oval-shaped dome associated with or without untreated serous retinal detachment.

Methods
Twenty-eight patients with high myopia (40 eyes) with smooth macular elevations related to a vertical oval-shaped dome were recruited. Serous retinal detachment was investigated; 11 eyes had persistent submacular fluid (study group) and 29 eyes lacked submacular fluid (control group). All patients underwent complete ophthalmological examinations, including optical coherence tomography at baseline every 6 months for 2 years. Fluorescein angiographies were performed in cases with serous retinal detachment to rule out choroidal neovascularisation.

Results
There were no statistical differences in baseline age, sex, spherical equivalence or axial length between the two groups. Serous retinal detachment always occurred at the top of the inward macular incurvation. Moreover, no statistically significant differences in mean best-corrected visual acuity were observed during the 24-month follow-up period in the study and control groups and between the two groups at all time points. The mean central foveal thickness was significantly higher in the study group at each visit (p=0.001, in all cases). At the final follow-up visit, complete resolution of the serous retinal detachment was achieved in 1 of the 11 study group’s eyes.

Conclusions
Serous retinal detachment is a complication associated with vertical oval-shaped domes that seems to remain stable in terms of visual function over time without treatment.
Managing antibiotics wisely: a quality improvement programme in a tertiary neonatal unit in the UK
Authors: Makri Vasiliki , Davies Gemma , Cannell Stephanie , Willson Katherine , Winterson Lucy , Webb Joanna , Kandhari Amit , Mansour Maha , Thomas Joanne , Morris Geraint , Matthes Jean , Banerjee Sujoy 
Published: May 2018

Microbial resistance to antibiotics is a serious global health problem compounded by antibiotic overuse and limited investment in new antibiotic research. Inappropriate perinatal antibiotic exposure is increasingly linked to lifelong adverse outcomes through its impact on the developing microbiome. Antibiotic stewardship may be the only effective preventative strategy currently available. As the first tertiary neonatal unit in the UK to collaborate in an international quality improvement programme (QIP) with Vermont Oxford Network (VON), we present the results of our antibiotic stewardship initiative.The QIP was officially launched in January 2016 and aimed to reduce antibiotic usage rate (AUR) by 20% of baseline by 31st December 2016 without compromising patient safety. A multidisciplinary team of professionals and parent representatives shared good practices and improvement strategies through international webinars and local meetings, devised uniform data collection methodology and implemented a number of carefully selected ‘Plan–Do–Study–Act’ cycles. Run charts were used to present data and, where appropriate, statistical analysis undertaken to compare outcomes.The QIP resulted in a sustained reduction in AUR from a baseline median of 347 to 198 per 1000 patient-days (a reduction of 43%). The proportion of culture-negative sepsis screens where antibiotics were stopped within 36–48 hours increased consistently from a baseline of 32.5% to 91%. The antibiotic days per patient at discharge reduced from a median of 3 to 2 days, and there was a reduction in practice variation. Our annual mortality and necrotising enterocolitis rates for the VON cohort (<30 weeks or <1500 g) were the best ever recorded, 5.5% and 1.4%, respectively. Audits confirmed a high level of staff and family awareness of the QIP.The QIP achieved a sustained reduction in antibiotic use without compromising patient safety. Our challenge is to sustain this improvement safely.
Examining lung cancer risks across different industries and occupations in Ontario, Canada: the establishment of the Occupational Disease Surveillance System
Authors: Jung James K H , Feinstein Saul G , Palma Lazgare Luis , Macleod Jill S , Arrandale Victoria H , McLeod Christopher B , Peter Alice , Demers Paul A 
Published: May 2018

BackgroundThe Occupational Disease Surveillance System (ODSS) was established in Ontario, Canada by linking a cohort of workers with data created from Workplace Safety and Insurance Board (WSIB) claims to administrative health databases. The aim of this study was to use ODSS to identify high-risk industry and occupation groups for lung cancer in Ontario.MethodsWorkers in the WSIB lost time claims database were linked to the Ontario Cancer Registry using subjects’ health insurance numbers, name, sex, birthdate and death date (if applicable). Several occupations and industries known to be at increased risk were outlined a priori to examine whether ODSS could replicate these associations. Age-adjusted, sex-stratified Cox proportional hazard models compared the risk of lung cancer within one industry/occupation versus all other groups in the cohort. Workers with a lung cancer diagnosis prior to cohort entry were excluded for analysis, leaving 2 187 762 workers for analysis.ResultsDuring the 1983 to 2014 follow-up, 34 661 workers in the cohort were diagnosed with lung cancer. Among expected high-risk industries, elevated risks were observed among workers in quarries/sand pits and construction industries for both sexes, and among males in metal mines, iron foundries, non-metallic mineral products industries and transportation industries. Excess risk was also observed among occupations in drilling/blasting, other mining/quarrying, mineral ore treating, excavating/grading/paving, truck driving, painting, bus driving and construction.ConclusionsThis current surveillance system identified several established high-risk groups for lung cancer and could be used for ongoing surveillance of occupational lung cancer in Ontario.
A Method of Deep Belief Network Image Classification Based on Probability Measure Rough Set Theory
Authors: Zhang Wenyu , Ren Lu , Wang Lei 
Published: May 2018

The increasing diverse demand for image feature recognition and complicated relationships among image pixels cannot be fully and effectively handled by traditional single image recognition methods. In order to effectively improve classification accuracy in image processing, a deep belief network (DBN) classification model based on probability measure rough set theory is proposed in our research. First, the incomplete and inaccurate fuzzy information in the original image is preprocessed by the rough set method based on probability measure. Second, the attribute features of the image information are extracted, the attribute feature set is reduced to generate the classification rules, and key components are extracted as the input of the DBN. Third, the network structure of the DBN is determined by the extracted classification rules, and the importance of the rough set attributes is integrated and the weights of the neuronal nodes are corrected by the backpropagation (BP) algorithm. Last, the DBN is trained to classify images. The experimental analysis of the proposed method for medical imagery shows that it is more effective than current single rough set approach or the taxonomy of deep learning.
HLA Class I and II Diversity Contributes to the Etiologic Heterogeneity of Non-Hodgkin Lymphoma Subtypes
Authors: Wang Sophia S. , Carrington Mary , Berndt Sonja I. , Slager Susan L. , Bracci Paige M. , Voutsinas Jenna , Cerhan James R. , Smedby Karin E. , Hjalgrim Henrik , Vijai Joseph , Morton Lindsay M. , Vermeulen Roel , Paltiel Ora , Vajdic Claire M. , Linet Martha S. , Nieters Alexandra , de Sanjose Silvia , Cozen Wendy , Brown Elizabeth E. , Turner Jennifer , Spinelli John J. , Zheng Tongzhang , Birmann Brenda M. , Flowers Christopher R. , Becker Nikolaus , Holly Elizabeth A. , Kane Eleanor , Weisenburger Dennis , Maynadie Marc , Cocco Pierluigi , Albanes Demetrius , Weinstein Stephanie J. , Teras Lauren R. , Diver W. Ryan , Lax Stephanie J. , Travis Ruth C. , Kaaks Rudolph , Riboli Elio , Benavente Yolanda , Brennan Paul , McKay James , Delfau-Larue Marie-Hélène , Link Brian K. , Magnani Corrado , Ennas Maria Grazia , Latte Giancarlo , Feldman Andrew L. , Doo Nicole Wong , Giles Graham G. , Southey Melissa C. , Milne Roger L. , Offit Kenneth , Musinsky Jacob , Arslan Alan A. , Purdue Mark P. , Adami Hans-Olov , Melbye Mads , Glimelius Bengt , Conde Lucia , Camp Nicola J. , Glenn Martha , Curtin Karen , Clavel Jacqueline , Monnereau Alain , Cox David G. , Ghesquières Hervé , Salles Gilles , Bofetta Paulo , Foretova Lenka , Staines Anthony , Davis Scott , Severson Richard K. , Lan Qing , Brooks-Wilson Angela , Smith Martyn T. , Roman Eve , Kricker Anne , Zhang Yawei , Kraft Peter , Chanock Stephen J. , Rothman Nathaniel , Hartge Patricia , Skibola Christine F. 
Published: May 2018

Abstract
A growing number of loci within the human leukocyte antigen (HLA) region have been implicated in non-Hodgkin lymphoma (NHL) etiology. Here, we test a complementary hypothesis of “heterozygote advantage” regarding the role of HLA and NHL, whereby HLA diversity is beneficial and homozygous HLA loci are associated with increased disease risk. HLA alleles at class I and II loci were imputed from genome-wide association studies (GWAS) using SNP2HLA for 3,617 diffuse large B-cell lymphomas (DLBCL), 2,686 follicular lymphomas (FL), 2,878 chronic lymphocytic leukemia/small lymphocytic lymphomas (CLL/SLL), 741 marginal zone lymphomas (MZL), and 8,753 controls of European descent. Both DLBCL and MZL risk were elevated with homozygosity at class I HLA-B and -C loci (OR DLBCL = 1.31, 95% CI = 1.06–1.60; OR MZL = 1.45, 95% CI = 1.12–1.89) and class II HLA-DRB1 locus (OR DLBCL = 2.10, 95% CI = 1.24–3.55; OR MZL = 2.10, 95% CI = 0.99–4.45). Increased FL risk was observed with the overall increase in number of homozygous HLA class II loci (P trend &lt; 0.0001, FDR = 0.0005). These results support a role for HLA zygosity in NHL etiology and suggests that distinct immune pathways may underly the etiology of the different NHL subtypes.
Significance: HLA gene diversity reduces risk for non-Hodgkin lymphoma. Cancer Res; 78(14); 4086–96. ©2018 AACR.
Nuclear IGF1R Interacts with Regulatory Regions of Chromatin to Promote RNA Polymerase II Recruitment and Gene Expression Associated with Advanced Tumor Stage
Authors: Aleksic Tamara , Gray Nicki , Wu Xiaoning , Rieunier Guillaume , Osher Eliot , Mills Jack , Verrill Clare , Bryant Richard J. , Han Cheng , Hutchinson Kathryn , Lambert Adam G. , Kumar Rajeev , Hamdy Freddie C. , Weyer-Czernilofsky Ulrike , Sanderson Michael P. , Bogenrieder Thomas , Taylor Stephen , Macaulay Valentine M. 
Published: May 2018

Abstract
Internalization of ligand-activated type I IGF receptor (IGF1R) is followed by recycling to the plasma membrane, degradation or nuclear translocation. Nuclear IGF1R reportedly associates with clinical response to IGF1R inhibitory drugs, yet its role in the nucleus is poorly characterized. Here, we investigated the significance of nuclear IGF1R in clinical cancers and cell line models. In prostate cancers, IGF1R was predominantly membrane localized in benign glands, while malignant epithelium contained prominent internalized (nuclear/cytoplasmic) IGF1R, and nuclear IGF1R associated significantly with advanced tumor stage. Using ChIP-seq to assess global chromatin occupancy, we identified IGF1R–binding sites at or near transcription start sites of genes including JUN and FAM21, most sites coinciding with occupancy by RNA polymerase II (RNAPol2) and histone marks of active enhancers/promoters. IGF1R was inducibly recruited to chromatin, directly binding DNA and interacting with RNAPol2 to upregulate expression of JUN and FAM21, shown to mediate tumor cell survival and IGF-induced migration. IGF1 also enriched RNAPol2 on promoters containing IGF1R–binding sites. These functions were inhibited by IGF1/II–neutralizing antibody xentuzumab (BI 836845), or by blocking receptor internalization. We detected IGF1R on JUN and FAM21 promoters in fresh prostate cancers that contained abundant nuclear IGF1R, with evidence of correlation between nuclear IGF1R content and JUN expression in malignant prostatic epithelium. Taken together, these data reveal previously unrecognized molecular mechanisms through which IGFs promote tumorigenesis, with implications for therapeutic evaluation of anti-IGF drugs.
Significance: These findings reveal a noncanonical nuclear role for IGF1R in tumorigenesis, with implications for therapeutic evaluation of IGF inhibitory drugs. Cancer Res; 78(13); 3497–509. ©2018 AACR.