bluuebunny/crossref_metadata_2025_split huggingface dataset:
Seek
TB, a Two-Stage Multiplex Real-Time-PCR-Based Method for Differentiation of the Mycobacterium tuberculosis Complex
Authors: Reddington Kate , Zumla Alimuddin , Bates Matthew , van Soolingen Dick , Niemann Stefan , Barry Thomas , O'Grady Justin 
Published: May 2012

ABSTRACT

Tuberculosis (TB) in humans is caused by members of the
Mycobacterium tuberculosis
complex (MTC). The accurate identification of the MTC member causing human infection is important because the treatment of TB caused by some MTC members requires an alteration of the standard drug regimen, it can inform whether transmission is human to human or zoonotic, and it enables accurate epidemiology studies that help improve TB control. In this study, an internally controlled two-stage multiplex real-time PCR-based method,
Seek
TB, was developed for the accurate identification of all members of the MTC. The method was tested against a panel of well-characterized bacterial strains (
n
= 180) and determined to be 100% specific for members of the MTC. Additionally, 125 Mycobacteria Growth Indicator Tube (MGIT)-positive cultures were blindly tested by using
Seek
TB, and the results were compared to those of the GenoType MTBC and TBc ID tests. The
Seek
TB and GenoType MTBC results were 100% concordant, identifying 84 of these isolates as
M. tuberculosis
isolates and 41 as non-MTC isolates. Nine discordant results between the molecular methods and the TBc ID culture confirmation test were observed; however, nucleotide sequencing confirmed the results obtained with GenoType MTBC and
Seek
TB.
Seek
TB is the first-described internally controlled multiplex real-time PCR diagnostic method for the accurate identification of all eight members of the MTC. This method, designed for use on cultured patient samples, is specific, sensitive, and rapid, with a turnaround time to results of approximately 1.5 to 3.5 h, depending on which, if any, member of the MTC is present.
Molecular and Culture-Based Assessment of the Microbial Diversity of Diabetic Chronic Foot Wounds and Contralateral Skin Sites
Authors: Oates Angela , Bowling Frank L. , Boulton Andrew J. M. , McBain Andrew J. 
Published: May 2012

ABSTRACT

Wound debridement samples and contralateral (healthy) skin swabs acquired from 26 patients attending a specialist foot clinic were analyzed by differential isolation and eubacterium-specific PCR-denaturing gradient gel electrophoresis (DGGE) in conjunction with DNA sequencing. Thirteen of 26 wounds harbored pathogens according to culture analyses, with
Staphylococcus aureus
being the most common (13/13). Candida (1/13), pseudomonas (1/13), and streptococcus (7/13) were less prevalent. Contralateral skin was associated with comparatively low densities of bacteria, and overt pathogens were not detected. According to DGGE analyses, all wounds contained significantly greater eubacterial diversity than contralateral skin (
P
< 0.05), although no significant difference in total eubacterial diversity was detected between wounds from which known pathogens had been isolated and those that were putatively uninfected. DGGE amplicons with homology to
Staphylococcus
sp. (8/13) and
S. aureus
(2/13) were detected in putatively infected wound samples, while
Staphylococcus
sp. amplicons were detected in 11/13 noninfected wounds;
S. aureus
was not detected in these samples. While a majority of skin-derived DGGE consortial fingerprints could be differentiated from wound profiles through principal component analysis (PCA), a large minority could not. Furthermore, wounds from which pathogens had been isolated could not be distinguished from putatively uninfected wounds on this basis. In conclusion, while chronic wounds generally harbored greater eubacterial diversity than healthy skin, the isolation of known pathogens was not associated with qualitatively distinct consortial profiles or otherwise altered diversity. The data generated support the utility of both culture and DGGE for the microbial characterization of chronic wounds.
Cation Concentration Variability of Four Distinct Mueller-Hinton Agar Brands Influences Polymyxin B Susceptibility Results
Authors: Girardello Raquel , Bispo Paulo J. M. , Yamanaka Tiago M. , Gales Ana C. 
Published: May 2012

ABSTRACT

Polymyxins have been the only alternative therapeutic option for the treatment of serious infections caused by multidrug-resistant
Acinetobacter baumannii
or
Pseudomonas aeruginosa
isolates. For this reason, it is of crucial importance that susceptibility tests provide accurate results when testing these drug-pathogen combinations. In this study, the effect of cation concentration variability found on different commercial brands of Mueller-Hinton agar (MHA) for testing polymyxin B susceptibility was evaluated. The polymyxin B susceptibilities determined using Etest and disk diffusion were compared to those determined by the CLSI reference broth microdilution method. In general, the polymyxin B MIC values were higher when determined by Etest than when determined by broth microdilution against both
A. baumannii
and
P. aeruginosa
isolates. A high very major error rate (10%) was observed, as well as a trend toward lower MICs, compared to those determined by broth microdilution when the Merck MHA was tested by Etest. Poor essential agreement rates (10 to 70%) were observed for
P. aeruginosa
when all MHA brands were tested by Etest. Although an excellent categorical agreement rate (100%) was seen between the disk diffusion and broth microdilution methods for
P. aeruginosa
, larger zones of inhibition were shown obtained using the Merck MHA. The high cation concentration variability found for the MHA brands tested correlated to the low accuracy, and discrepancies in the polymyxin B MICs were determined by Etest method, particularly for
P. aeruginosa
isolates.
Transfer of the UAP56 Interaction Motif of Human Cytomegalovirus pUL69 to Its Murine Cytomegalovirus Homolog Converts the Protein into a Functional mRNA Export Factor That Can Substitute for pUL69 during Viral Infection
Authors: Zielke Barbara , Wagenknecht Nadine , Pfeifer Caroline , Zielke Katrin , Thomas Marco , Stamminger Thomas 
Published: May 2012

ABSTRACT
Nucleocytoplasmic shuttling and interaction with the cellular mRNA export factor UAP56 are prerequisites for the mRNA export activity of human cytomegalovirus (HCMV) pUL69. Although the murine cytomegalovirus homolog pM69 shuttles, it fails to export mRNAs due to its inability to recruit UAP56. However, chimeric proteins comprising pM69 fused to N-terminal pUL69 fragments, including its UAP56 interaction motif, acquire mRNA export activity. Importantly, growth curves of recombinant HCMVs illustrate that such a chimeric protein, but not pM69, substitutes for pUL69 during HCMV infection.
Endogenous Hepadnaviruses in the Genome of the Budgerigar (Melopsittacus undulatus) and the Evolution of Avian Hepadnaviruses
Authors: Cui Jie , Holmes Edward C. 
Published: May 2012

ABSTRACT
Endogenous hepadnaviruses (hepatitis B viruses [HBVs]) were recently discovered in the genomes of passerine birds. We mined six additional avian genomes and discovered multiple copies of endogenous HBVs in the budgerigar (order Psittaciformes), designated eBHBV. A phylogenetic analysis reveals that the endogenous hepadnaviruses are more diverse than their exogenous counterparts and that the endogenous and exogenous hepadnaviruses form distinct lineages even when sampled from the same avian order, indicative of multiple genomic integration events.
Immune Selection
In Vitro
Reveals Human Immunodeficiency Virus Type 1 Nef Sequence Motifs Important for Its Immune Evasion Function
In Vivo
Authors: Lewis Martha J. , Lee Patricia , Ng Hwee L. , Yang Otto O. 
Published: May 2012

ABSTRACT

Human immunodeficiency virus type 1 (HIV-1) Nef downregulates major histocompatibility complex class I (MHC-I), impairing the clearance of infected cells by CD8
+
cytotoxic T lymphocytes (CTLs). While sequence motifs mediating this function have been determined by
in vitro
mutagenesis studies of laboratory-adapted HIV-1 molecular clones, it is unclear whether the highly variable Nef sequences of primary isolates
in vivo
rely on the same sequence motifs. To address this issue,
nef
quasispecies from nine chronically HIV-1-infected persons were examined for sequence evolution and altered MHC-I downregulatory function under Gag-specific CTL immune pressure
in vitro
. This selection resulted in decreased
nef
diversity and strong purifying selection. Site-by-site analysis identified 13 codons undergoing purifying selection and 1 undergoing positive selection. Of the former, only 6 have been reported to have roles in Nef function, including 4 associated with MHC-I downregulation. Functional testing of naturally occurring
in vivo
polymorphisms at the 7 sites with no previously known functional role revealed 3 mutations (A84D, Y135F, and G140R) that ablated MHC-I downregulation and 3 (N52A, S169I, and V180E) that partially impaired MHC-I downregulation. Globally, the CTL pressure
in vitro
selected functional Nef from the
in vivo
quasispecies mixtures that predominately lacked MHC-I downregulatory function at the baseline. Overall, these data demonstrate that CTL pressure exerts a strong purifying selective pressure for MHC-I downregulation and identifies novel functional motifs present in Nef sequences
in vivo
.
Hemorrhagic complications after prasugrel (Effient) therapy for vascular neurointerventional procedures
Authors: Akbari S Hassan , Reynolds Matthew R , Kadkhodayan Yasha , Cross DeWitte T , Moran Christopher J 
Published: May 2012

IntroductionDual antiplatelet therapy (DAPT) with aspirin and a thienopyridine (eg, clopidogrel) prevents stent related thromboembolic events in cardiac patients and is frequently utilized during neurointerventional surgery. However, recent data suggest that many patients exhibit clopidogrel resistance. Prasugrel—a newer thienopyridine—lowers the rate of cardiac stent thromboses in clopidogrel non-responders but a paucity of data exist regarding its safety and efficacy in neurointerventional surgery.MethodsAll patients undergoing neurointerventional surgery by a single interventionalist (CJM) over a 20 month period were retrospectively identified. Charts were reviewed for pre- and post-procedural DAPT regimens, pre-procedural coagulation parameters and procedural complications.Results76 patients received pre- and post-procedural DAPT for endovascular treatment of an intracerebral aneurysm, dural arteriovenous fistula or intra/extracranial arterial stenosis. 51 patients underwent 55 total procedures and were treated with aspirin/clopidogrel; 25 patients underwent 31 total procedures and were treated with aspirin/prasugrel. Those patients who received aspirin/prasugrel DAPT were identified pre-procedurally to be clopidogrel non-responders. Both treatment groups had a similar percentage of patients undergoing aneurysm coiling, stent assisted aneurysm coiling, aneurysm Onyx embolization, aneurysm pipeline embolization device treatment, extra/intracranial carotid artery angioplasty and stenting, and dural arteriovenous fistula coil embolization. A total of eight (9.3%) hemorrhagic complications were observed, two (3.6%) in the aspirin/clopidogrel group and six (19.4%) in the aspirin/prasugrel group (p=0.02). No differences were noted in hemorrhage rates for each procedure between treatment groups, nor were there any differences in thrombotic complications between groups.ConclusionOur results suggest that DAPT with aspirin/prasugrel may predispose to a higher risk of hemorrhage during neurointerventional surgery compared with DAPT with aspirin/clopidogrel.
Substratum control on tunnel-valley formation in Denmark
Authors: Sandersen Peter B. E. , Jørgensen Flemming 
Published: May 2012

Abstract
Tunnel valleys formed by meltwater erosion underneath the margins of the Pleistocene ice sheets are present in high numbers in the Danish onshore area. The geographical distribution of the buried tunnel valleys is uneven, but when comparing with the substrata lithology we find a large number of valleys in areas dominated by low-permeable sediment and a smaller number in areas with highly permeable substrata. The observations point to the drainage capacity of the ice-sheet substratum as an important factor controlling tunnel-valley formation. Tunnel-valley formation appears to be favoured in areas with low-permeable substrata because meltwater drainage through the sediments is impeded, leading to the formation of a channelized subglacial drainage system. The high transmissivity in areas dominated by permeable substrata facilitates drainage of a part of the meltwater as groundwater. This causes a lowering of the subglacial meltwater pressures, and tunnel-valley formation is less likely. Once formed and filled, the tunnel valleys cause a change of the hydraulic properties of the substratum and if subglacial water pressures underneath a subsequent ice advance are sufficiently high, old tunnel valleys will be prone to reactivation.
Multistage erosion and infill of buried Pleistocene tunnel valleys and associated seismic velocity effects
Authors: Kristensen T. B. , Huuse M. 
Published: May 2012

Abstract
This study provides results on buried tunnel valleys from the greatest number of released three-dimensional (3D) seismic surveys in the Danish North Sea sector to date. The valley infill sediments and the fluid content from buried Pleistocene tunnel valleys beneath the North Sea floor cause significant seismic velocity effects. Analysis of conventional 3D seismic data, high-resolution two-dimensional (2D) seismic data and wire-line log data from exploration wells reveal a multistage cut-and-fill history of tunnel valleys in the Danish North Sea. The seismic infill facies of the valleys is analysed and the associated velocity effects quantified. The valley infill generates both velocity pull up and push down of underlying seismic horizons. In contrast to expectations, our analysis shows no distinct correlation between particular seismic facies and a particular travel-time effect. Infill units characterized by the same seismic facies within the same valley can thus provide different travel-time effects. The anomalous velocities can be used as indicators of shallow gas and till content within the valleys leading to low and high velocities, respectively. Detailed investigations suggest that tunnel valley formation and sediment infill occurred over several episodes, with partial reuse of the kilometre-scale valleys and strong indications of ice-free periods between some of the formation episodes.
Neoproterozoic deglacial sediments and their hydrocarbon source rock potential
Authors: Le Heron Daniel Paul , Craig Jonathan 
Published: May 2012

Abstract
Many Neoproterozoic successions contain viable hydrocarbon source rocks, even though they were deposited before most extant life forms evolved. Eukaryotic microalgae, bacteria, chlorophyte micoalgae, marine pelagophyte algae and dinoflagellates may have contributed organic matter. Major global-scale glaciations, which are commonly attributed to a ‘snowball’ or ‘slushball’ Earth scenario, or deposited under a ‘zipper rift’ scenario, are believed to have played an important role in the deposition of hydrocarbon source rocks during the mid- Neoproterozoic (Cryogenian). Phases of Cryogenian deglaciation may have culminated in the deposition of high total organic carbon shales and ‘cap carbonates’ in restricted anoxic basins, which may have been carved by ice sheets themselves or, alternatively, formed as restricted extensional half graben as Rodinia began to fragment. One example of these organically enriched deglacial sediments comprises shales and dolostones deposited following the Sturtian glaciation in the Centralian Superbasin of Australia, an amalgam of basins that extends almost continent-wide across Australia. Data from the Marmot MMDD-1 drill core on the Stuart Shelf in the southern part of the Centralian Superbasin, together with previously published data on organic enrichment in the Amadeus Basin in the central part of the Centralian Superbasin, suggest that the deposition of organically enriched shales was widespread during the Sturtian deglaciation.
Regional Cell Proliferation in Microdissected Human Prostate Specimens after Heavy Water Labeling In Vivo: Correlation with Prostate Epithelial Cells Isolated from Seminal Fluid
Authors: Hayes Gregory M. , Simko Jeff , Holochwost Daniel , Kuchinsky Kyle , Busch Robert , Misell Lisa , Murphy Elizabeth J. , Carroll Peter , Chan June , Shinohara Katsuto , Hellerstein Marc K. 
Published: May 2012

Abstract
Purpose: Prostate cancer is detected with increasing frequency but has a highly variable natural history and prognosis and active surveillance of men with low-risk prostate cancer would benefit greatly from minimally invasive methods to identify progression. We describe here two novel in vivo metrics of cell proliferation in men with prostate neoplasia.
Experimental Design: Three groups of men drank heavy water, a nonradioactive, stable isotopic tracer for 14 to 28 days: (i) healthy men, (ii) men scheduled for transrectal core needle biopsy, and (iii) men scheduled for radical prostatectomy. Prostate epithelial cells (PEC) were isolated from ejaculated seminal fluid in all subjects. Histologically graded lesions were microdissected from tissue slides obtained from subjects undergoing surgery and proliferation rates were measured from isolated cells via mass spectrometry.
Results: Proliferation rates of seminal PEC in healthy men (0.10%–0.27%/d) were stable on repeat sampling. Rates above 0.34%/d were seen only in patients with cancer where rates increased progressively from normal tissue through benign prostate hyperplasia, prostate intraepithelial neoplasia, and tumor grades III and IV in all subjects. Seminal PEC kinetics correlated highly with the most proliferative microdissected region in each subject (r2 = 0.94).
Conclusions: Prostate cell proliferation can be measured in vivo from microdissected histopathology sections or noninvasively from seminal fluid where the latter reflects the most proliferative region of the gland. This approach may allow monitoring of progression in men with low-risk prostate cancer. Clin Cancer Res; 18(12); 3250–60. ©2012 AACR.
ErbB3 Inhibitory Surrobodies Inhibit Tumor Cell Proliferation In Vitro and In Vivo
Authors: Foreman Pamela K. , Gore Medini , Kobel Philip A. , Xu Li , Yee Helena , Hannum Charles , Ho Hoangdung , Wang Sandra M. , Tran Hieu V. , Horowitz Michael , Horowitz Lawrence , Bhatt Ramesh R. 
Published: May 2012

Abstract
ErbB3 is an important regulator of tumorigenesis and is implicated in development of resistance to several currently used oncology drugs. We have identified ErbB3 inhibitors based on a novel biologic scaffold termed a surrobody. Two of these inhibitors appear to work by a previously unrecognized mechanism of action. As a consequence, they not only inhibited cell proliferation and intracellular signaling driven by stimulation with the ErbB3 ligand neuregulin (NRG), but also inhibited signaling and proliferation that was driven by overexpression of ErbB2 in the absence of ligand stimulation. In addition, the surrobodies inhibited tumor growth in vivo in both ErbB2-overexpressing and nonoverexpressing cells. In ErbB2-overexpressing cells, both of the anti-ErbB3 surrobodies significantly augmented the activities of trastuzumab, lapatinib, and GDC-0941, agents that inhibit cell proliferation by different mechanisms. Moreover, although NRG diminished the efficacy of these agents, when they were combined with anti-ErbB3 surrobodies the affect of NRG was abrogated. In this capacity, the anti-ErbB3 surrobodies were more effective than the ErbB2/ErbB3 dimerization inhibitory antibody pertuzumab. Despite the fact that these surrobodies appear to engage ErbB3 differently than previously described anti-ErbB3 antibodies, they retain all of the beneficial characteristics of this class of agents, including the ability to augment drugs that inhibit EGF receptor. These anti-ErbB3 agents, therefore, show substantial promise for development as single agents or in combination with other ErbB-directed antibodies or small molecules and may provide for a broader range of therapeutic indications than previously described anti-ErbB3 antibodies. Mol Cancer Ther; 11(7); 1411–20. ©2012 AACR.
A Study of Prostaglandin Pathway Genes and Interactions with Current Nonsteroidal Anti-inflammatory Drug Use in Colorectal Adenoma
Authors: Edwards Todd L. , Shrubsole Martha J. , Cai Qiuyin , Li Guoliang , Dai Qi , Rex Douglas K. , Ulbright Thomas M. , Fu Zhenming , Murff Harvey J. , Smalley Walter , Ness Reid , Zheng Wei 
Published: May 2012

Abstract
Colorectal cancer (CRC) is the second leading cause of cancer-related death and usually arises from colorectal polyps. Screening and removal of polyps reduce mortality from CRC. Colorectal polyps are known to aggregate in families; however the genetic determinants for risk of polyps are unknown. In addition, it has been shown that nonsteroidal anti-inflammatory drug (NSAID) use decreases the risk of CRC and the incidence and size of polyps. In this study, we used data from the Tennessee Colorectal Polyp Study and the Tennessee–Indiana Adenoma Recurrence Study to evaluate selected genes from the prostaglandin (PG) metabolism and signaling pathways for association with risk of polyps and for interactions with NSAIDs. Our design consisted of discovery and replication phases for a total of 2,551 Caucasian polyp cases and 3,285 Caucasian controls. We carried out multivariable logistic regression to test for association in both the discovery and replication phase and further examined the results with meta-analysis. We detected association signals in the genes PGE receptor 3 (PTGER3) and 15-hydroxyprostaglandin dehydrogenase (HPGD), both strong biologic candidates for influence on polyp risk. We did not observe the previously reported effects and effect modification in PG–endoperoxide synthase 2 (PTGS2), PGE receptor 2 (PTGER2), or PGE receptor 4 (PTGER4), although we did observe a single nucleotide polymorphism in PTGER2 associated with risk of multiple adenomas. We also observed effect modification of the HPGD signal by NSAID exposure. Cancer Prev Res; 5(6); 855–63. ©2012 AACR.