bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of Single and Combined Antibiotic Treatments of Anthrax in Rabbits
Authors: Weiss Shay , Altboum Zeev , Glinert Itai , Schlomovitz Josef , Sittner Assa , Bar-David Elad , Kobiler David , Levy Haim 
Published: September 2015

ABSTRACT

Respiratory anthrax is a fatal disease in the absence of early treatment with antibiotics. Rabbits are highly susceptible to infection with
Bacillus anthracis
spores by intranasal instillation, succumbing within 2 to 4 days postinfection. This study aims to test the efficiency of antibiotic therapy to treat systemic anthrax in this relevant animal model. Delaying the initiation of antibiotic administration to more than 24 h postinfection resulted in animals with systemic anthrax in various degrees of bacteremia and toxemia. As the onset of symptoms in humans was reported to start on days 1 to 7 postexposure, delaying the initiation of treatment by 24 to 48 h (time frame for mass distribution of antibiotics) may result in sick populations. We evaluated the efficacy of antibiotic administration as a function of bacteremia levels at the time of treatment initiation. Here we compare the efficacy of treatment with clarithromycin, amoxicillin-clavulanic acid (Augmentin), imipenem, vancomycin, rifampin, and linezolid to the previously reported efficacy of doxycycline and ciprofloxacin. We demonstrate that treatment with amoxicillin-clavulanic acid, imipenem, vancomycin, and linezolid were as effective as doxycycline and ciprofloxacin, curing rabbits exhibiting bacteremia levels of up to 10
5
CFU/ml. Clarithromycin and rifampin were shown to be effective only as a postexposure prophylactic treatment but failed to treat the systemic (bacteremic) phase of anthrax. Furthermore, we evaluate the contribution of combined treatment of clindamycin and ciprofloxacin, which demonstrated improvement in efficacy compared to ciprofloxacin alone.
In Vitro
Activity of Simeprevir against Hepatitis C Virus Genotype 1 Clinical Isolates and Its Correlation with NS3 Sequence and Site-Directed Mutants
Authors: Verbinnen Thierry , Fevery Bart , Vijgen Leen , Jacobs Tom , De Meyer Sandra , Lenz Oliver 
Published: September 2015

ABSTRACT

Simeprevir (TMC435) is a once-daily, single-pill, oral hepatitis C virus (HCV) NS3 protease inhibitor approved for the treatment of chronic HCV infection. Phenotypic characterization of baseline isolates and isolates from HCV genotype 1-infected patients failing with a simeprevir-based regimen was performed using chimeric replicons carrying patient-derived NS3 protease sequences. Cutoff values differentiating between full susceptibility to simeprevir (≤2.0-fold reduction in simeprevir activity) and low-level versus high-level resistance (≥50-fold reduction in simeprevir activity) were determined. The median simeprevir fold change in the 50% effective concentration (FC) of pretreatment genotype 1a isolates, with and without Q80K, and genotype 1b isolates was 11, 0.9, and 0.4, respectively. Naturally occurring NS3 polymorphisms that reduced simeprevir activity, other than Q80K, were uncommon in the simeprevir studies and generally conferred low-level resistance
in vitro
. Although the proportion of patients with failure differed by HCV geno/subtype and/or presence of baseline Q80K, the level of simeprevir resistance observed at failure was similarly high irrespective of type of failure, HCV genotype 1 subtype, and presence or absence of baseline Q80K. At the end of the study, simeprevir activity against isolates that lost the emerging amino acid substitution returned to pretreatment values. Activity of simeprevir against clinical isolates and site-directed mutant replicons harboring the corresponding single or double amino acid substitutions correlated well, showing that simeprevir resistance can be attributed to these substitutions. In conclusion, pretreatment NS3 isolates were generally fully susceptible (FC, ≤2.0) or conferred low-level resistance to simeprevir
in vitro
(FC, >2.0 and <50). Treatment failure with a simeprevir-based regimen was associated with emergence of high-level-resistance variants (FC, ≥50).
Effect of Preexposure to Triazoles on Susceptibility and Virulence of Rhizopus oryzae
Authors: Bellanger Anne-Pauline , Albert Nathaniel D. , Lewis Russell E. , Walsh Thomas J. , Kontoyiannis Dimitrios P. 
Published: September 2015

ABSTRACT

Triazole prophylaxis has become the norm in patients with hematological malignancies. Breakthrough infections caused by
Mucorales
during triazole prophylaxis remain a challenging problem. We found that preexposure of
Rhizopus oryzae
to antifungal triazoles (fluconazole, voriconazole, posaconazole, and itraconazole) did not modify the
in vitro
susceptibility of
Rhizopus oryzae
to posaconazole. In contrast, preexposure of
Rhizopus
to triazoles was associated with the enhanced
in vitro
susceptibility of
R. oryzae
to amphotericin B. Preexposure to posaconazole did not alter the virulence of
R. oryzae
in the fly model of mucormycosis.
Impact of Glycopeptide Resistance in Staphylococcus aureus on the Dalbavancin
In Vivo
Pharmacodynamic Target
Authors: Lepak A. , Marchillo K. , VanHecker J. , Andes D. 
Published: September 2015

ABSTRACT

Dalbavancin is a novel lipoglycopeptide with activity against
Staphylococcus aureus
, including glycopeptide-resistant isolates. The
in vivo
investigation reported here tested the effects of this antibiotic against seven
S. aureus
isolates with higher MICs, including several vancomycin-intermediate strains. Results of 1-log kill and 2-log kill were achieved against seven and six of the isolates, respectively. The mean free-drug area under the concentration-time curve (
f
AUC)/MIC values for net stasis, 1-log kill, and 2-log kill were 27.1, 53.3, and 111.1, respectively.
In Vitro
and Molecular Surveillance for Antimalarial Drug Resistance in Plasmodium falciparum Parasites in Western Kenya Reveals Sustained Artemisinin Sensitivity and Increased Chloroquine Sensitivity
Authors: Lucchi Naomi W. , Komino Franklin , Okoth Sheila Akinyi , Goldman Ira , Onyona Philip , Wiegand Ryan E. , Juma Elizabeth , Shi Ya Ping , Barnwell John W. , Udhayakumar Venkatachalam , Kariuki Simon 
Published: September 2015

ABSTRACT

Malaria control is hindered by the evolution and spread of resistance to antimalarials, necessitating multiple changes to drug policies over time. A comprehensive antimalarial drug resistance surveillance program is vital for detecting the potential emergence of resistance to antimalarials, including current artemisinin-based combination therapies. An antimalarial drug resistance surveillance study involving 203
Plasmodium falciparum
malaria-positive children was conducted in western Kenya between 2010 and 2013. Specimens from enrolled children were analyzed
in vitro
for sensitivity to chloroquine (CQ), amodiaquine (AQ), mefloquine (MQ), lumefantrine, and artemisinin derivatives (artesunate and dihydroartemisinin) and for drug resistance allele polymorphisms in
P. falciparum crt
(
Pfcrt
),
Pfmdr-1
, and the K13 propeller domain (K13). We observed a significant increase in the proportion of samples with the
Pfcrt
wild-type (CVMNK) genotype, from 61.2% in 2010 to 93.0% in 2013 (
P
< 0.0001), and higher proportions of parasites with elevated sensitivity to CQ
in vitro
. The majority of isolates harbored the wild-type N allele in
Pfmdr-1
codon 86 (93.5%), with only 7 (3.50%) samples with the N86
Y
mutant allele (the mutant nucleotide is underlined). Likewise, most isolates harbored the wild-type
Pfmdr-1
D1246 allele (79.8%), with only 12 (6.38%) specimens with the D1246
Y
mutant allele and 26 (13.8%) with mixed alleles. All the samples had a single copy of the
Pfmdr-1
gene (mean of 0.907 ± 0.141 copies). None of the sequenced parasites had mutations in K13. Our results suggest that artemisinin is likely to remain highly efficacious and that CQ sensitivity appears to be on the rise in western Kenya.
Identification and Biochemical Characterization of the Novel α2,3-Sialyltransferase WbwA from Pathogenic Escherichia coli Serotype O104
Authors: Czuchry Diana , Desormeaux Paul , Stuart Melissa , Jarvis Donald L. , Matta Khushi L. , Szarek Walter A. , Brockhausen Inka 
Published: September 2015

ABSTRACT

The sialyl-T antigen sialylα2-3Galβ1-3GalNAc is a common O-glycan structure in human glycoproteins and is synthesized by sialyltransferase ST3Gal1. The enterohemorrhagic
Escherichia coli
serotype O104 has the rare ability to synthesize a sialyl-T antigen mimic. We showed here that the
wbwA
gene of the
E. coli
O104 antigen synthesis gene cluster encodes an α2,3-sialyltransferase WbwA that transfers sialic acid from CMP-sialic acid to Galβ1-3GalNAcα-diphosphate-lipid acceptor. Nuclear magnetic resonance (NMR) analysis of purified WbwA enzyme reaction product indicated that the sialyl-T antigen sialylα2-3Galβ1-3GalNAcα-diphosphate-lipid was synthesized. We showed that the conserved His-Pro (HP) motif and Glu/Asp residues of two EDG motifs in WbwA are important for the activity. The characterization studies showed that WbwA from
E. coli
O104 is a monofunctional α2,3-sialyltransferase and is distinct from human ST3Gal1 as well as all other known sialyltransferases due to its unique acceptor specificity. This work contributes to knowledge of the biosynthesis of bacterial virulence factors.

IMPORTANCE
This is the first characterization of a sialyltransferase involved in the synthesis of an O antigen in
E. coli
. The enzyme contributes to the mimicry of human sialyl-T antigen and has unique substrate specificity but very little sequence identity to other sialyltransferases. Thus, the bacterial sialyltransferase is related to the human counterpart only by the similarity of biochemical activity.
Integrated Pathophysiology of Pyelonephritis
Authors: Choong Ferdinand X. , Antypas Haris , Richter-Dahlfors Agneta 
Published: September 2015

ABSTRACTPyelonephritis represents a subset of urinary tract infections that occur from bacteria ascending from the lower to the upper reaches of the genitourinary system, such as the kidney. The renal system contains a range of hydrodynamically and immunologically challenging, interconnected microenvironments where the invading pathogen may populate during the course of the infection. The situation at the infection foci changes dynamically, vacillating between bacterial colonization and clearance, to which the outcome is a summation of all host-pathogen elements in play. A selection of important determinants includes factors of microbial origin, effects of eukaryotic cell signaling, physiological facets of the infected organ, and signals from distal organs. Improved understanding of the multifactorial aspects of molecular pathogenesis of infection requires intravital, cross-disciplinary approaches with high spatio-temporal resolution. The advancement of such approaches promises to eventually provide a comprehensive understanding of the integrated pathophysiology of pyelonephritis.
Effectiveness of peer educators on the uptake of mobile X-ray tuberculosis screening at homeless hostels: a cluster randomised controlled trial
Authors: Aldridge Robert W , Hayward Andrew C , Hemming Sara , Possas Lucia , Ferenando Gloria , Garber Elizabeth , Lipman Marc , McHugh Timothy D , Story Alistair 
Published: September 2015

Trial designCluster randomised controlled trial.ObjectiveTo compare current practice for encouraging homeless people to be screened for tuberculosis on a mobile digital X-ray unit in London, UK, with the additional use of volunteer peer educators who have direct experience of tuberculosis, homelessness or both.Participants46 hostels took part in the study, with a total of 2342 residents eligible for screening. The study took place between February 2012 and October 2013 at homeless hostels in London, UK.InterventionAt intervention sites, volunteer peer educators agreed to a work plan that involved moving around the hostel in conjunction with the hostel staff, and speaking to residents in order to encourage them to attend the screening.RandomisationCluster randomisation (by hostel) was performed using an internet-based service to ensure allocation concealment, with minimisation by hostel size and historical screening uptake.BlindingOnly the study statistician was blinded to the allocation of intervention or control arms.Primary outcomeThe primary outcome was the number of eligible clients at a hostel venue screened for active pulmonary tuberculosis by the mobile X-ray unit.ResultsA total of 59 hostels were considered for eligibility and 46 were randomised. Control sites had a total of 1192 residents, with a median uptake of 45% (IQR 33–55). Intervention sites had 1150 eligible residents with a median uptake of 40% (IQR 25–61). Using Poisson regression to account for the clustered study design, hostel size and historical screening levels, there was no evidence that peer educators increased uptake (adjusted risk ratio 0.98; 95% CIs 0.80 to 1.20). The study team noted no adverse events.ConclusionsThis study found no evidence that volunteer peer educators increased client uptake of mobile X-ray unit screening for tuberculosis. Further qualitative work should be undertaken to explore the possible ancillary benefits to peer volunteers.Trial registration numberISRCTN17270334.
Mesozoic tectonic and topographic evolution of Central Asia and Tibet: a preliminary synthesis
Authors: Jolivet Marc 
Published: September 2015

Abstract
During the Late Palaeozoic–Mesozoic, Central Asia and Tibet were affected by several geodynamic episodes that induced either large-scale compression or widespread extension. The Late Palaeozoic final amalgamation of the Central Asian Orogenic Belt, the accretion of the Cimmerian blocks, the closure of the Mongol–Okhotsk Ocean and the accretion of the Neocimmerian blocks set the structural pattern of the continent. This Mesozoic tectonic heritage plays a first-order role in the localization and evolution of the Tertiary deformation of the continent. Similarly, large-scale Mesozoic topographic features are still preserved in Central Asia, where they form a non-negligible part of the present-day topography. This work aims at providing an overview of the major tectonic events that affected Central Asia and Tibet during the Late Palaeozoic and Mesozoic periods. The general topographic evolution of the continent is also described together with the accompanying climatic changes through time.
MWI-Sum
Authors: Baralis Elena , Cagliero Luca , Fiori Alessandro , Garza Paolo 
Published: September 2015

Multidocument summarization addresses the selection of a compact subset of highly informative sentences, i.e., the summary, from a collection of textual documents. To perform sentence selection, two parallel strategies have been proposed: (a) apply general-purpose techniques relying on data mining or information retrieval techniques, and/or (b) perform advanced linguistic analysis relying on semantics-based models (e.g., ontologies) to capture the actual sentence meaning. Since there is an increasing need for processing documents written in different languages, the attention of the research community has recently focused on summarizers based on strategy (a).
This article presents a novel multilingual summarizer, namely MWI-Sum (Multilingual Weighted Itemset-based Summarizer), that exploits an itemset-based model to summarize collections of documents ranging over the same topic. Unlike previous approaches, it extracts frequent weighted itemsets tailored to the analyzed collection and uses them to drive the sentence selection process. Weighted itemsets represent correlations among multiple highly relevant terms that are neglected by previous approaches. The proposed approach makes minimal use of language-dependent analyses. Thus, it is easily applicable to document collections written in different languages.
Experiments performed on benchmark and real-life collections, English-written and not, demonstrate that the proposed approach performs better than state-of-the-art multilingual document summarizers.
Environmental Burden of Traditional Bioenergy Use
Authors: Masera Omar R. , Bailis Rob , Drigo Rudi , Ghilardi Adrian , Ruiz-Mercado Ilse 
Published: September 2015

Approximately 40% of the global population relies on traditional bioenergy, accounting for 9% of global energy use and 55% of global wood harvest. However, knowledge about the environmental impacts of traditional bioenergy is fragmented. This review addresses several persistent questions and summarizes recent research on land cover change (LCC) and pollution emissions resulting from traditional bioenergy use. We also review recent studies analyzing transitions from traditional bioenergy to cleaner stoves and fuels.Between 27 and 34% of the wood fuel harvest in 2009 was unsustainable, with large geographical variations. Almost 300 million rural people live in wood fuel “hotspots,” concentrated in South Asia and East Africa, creating risks of wood-fuel-driven degradation. Different fuels and stoves show variation in climate-forcing emissions. Many, but not all, nontraditional stoves result in lower emissions than traditional models. Traditional bioenergy makes substantial contributions to anthropogenic black carbon (BC) emissions (18–30%) and small contributions to total anthropogenic climate impacts (2–8%). Transitions from traditional fuels and devices have proven difficult. Stacking, i.e., the use of multiple devices and fuels to satisfy household energy needs, is common, showing the need to shift stove interventions from the common approach that promotes one fuel and one device to integrated approaches that incorporate deep understanding of local needs and practices, and multiple fuels and devices, while monitoring residual use of traditional technologies.
The CBM Complex Underwrites NF-κB Activation to Promote HER2-Associated Tumor Malignancy
Authors: Pan Deng , Zhu Yifan , Zhou Zhicheng , Wang Tingting , You Harrison , Jiang Changying , Lin Xin 
Published: September 2015

Abstract
The HER2/Neu protein is overexpressed in a large fraction of human breast cancers. NF-κB is one of several transcription factors that are aberrantly activated in HER2-positive breast cancers; however, the molecular mechanism by which HER2 activates NF-κB remains unclear. The CARMA3–BCL10–MALT1 (CBM) complex is required for GPCR- and EGFR-induced NF-κB activation. In the current study, the role of the CBM complex in HER2-mediated NF-κB activation and HER2-positive breast cancer was investigated. Interestingly, HER2-mediated NF-κB activation requires protein kinase C (PKC) activity rather than AKT activity. Using biochemical and genetic approaches, it was shown that the CBM complex is required for HER2-induced NF-κB activation and functionally contributes to multiple properties of malignancy, such as proliferation, avoidance of apoptosis, migration, and invasion, both in vitro and in vivo. In addition, CARMA3-mediated NF-κB activity was required for the upregulation of two matrix metalloproteinases (MMP), MMP1 and MMP13, both of which contribute to tumor metastasis. To further access the physiologic role of CBM complex-mediated NF-κB activation in HER2-positive breast cancer progression, Malt1 knockout mice (Malt1−/−) were crossed with MMTV-Neu mice, in which mammary tumors spontaneously developed with HER2 overexpression. We observed delayed onset and prolonged progression time in mammary tumors in Malt1 knockout mice compared with control mice. In summary, these data demonstrate that the CBM complex is a crucial component mediating HER2-induced NF-κB signaling and tumor malignancy in HER2-positive breast cancer.
Implications: The CBM complex bridges key signaling pathways to confer malignant phenotypes and metastatic potential in HER2-associated breast cancer. Mol Cancer Res; 14(1); 93–102. ©2015 AACR.
NSAID Use and Risk of Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma: The Liver Cancer Pooling Project
Authors: Petrick Jessica L. , Sahasrabuddhe Vikrant V. , Chan Andrew T. , Alavanja Michael C. , Beane-Freeman Laura E. , Buring Julie E. , Chen Jie , Chong Dawn Q. , Freedman Neal D. , Fuchs Charles S. , Gaziano John Michael , Giovannucci Edward , Graubard Barry I. , Hollenbeck Albert R. , Hou Lifang , Jacobs Eric J. , King Lindsay Y. , Koshiol Jill , Lee I-Min , Linet Martha S. , Palmer Julie R. , Purdue Mark P. , Rosenberg Lynn , Schairer Catherine , Sesso Howard D. , Sigurdson Alice J. , Wactawski-Wende Jean , Zeleniuch-Jacquotte Anne , Campbell Peter T. , McGlynn Katherine A. 
Published: September 2015

Abstract
Chronic inflammation plays a pivotal role in the pathogenesis of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), the two most common types of liver cancer. A number of prior experimental studies have suggested that nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin and ibuprofen, may potentially protect against liver cancer. However, no observational study has examined the association between aspirin duration and dose or other over-the-counter non-aspirin NSAIDs, such as ibuprofen, and liver cancer incidence. Furthermore, the association between NSAID use and risk of ICC is unclear. As part of the Liver Cancer Pooling Project, we harmonized data on 1,084,133 individuals (HCC = 679, ICC = 225) from 10 U.S.-based prospective cohort studies. Cox proportional hazards regression models were used to evaluate multivariable-adjusted HRs and 95% confidence intervals (CI). Current aspirin use, versus nonuse, was inversely associated with HCC (HR, 0.68; 95% CI, 0.57–0.81), which persisted when restricted to individuals not using non-aspirin NSAIDs and in a 5- and 10-year lag analysis. The association between aspirin use and HCC risk was stronger for users who reported daily use, longer duration use, and lower dosage. Ibuprofen use was not associated with HCC risk. Aspirin use was associated with a reduced ICC risk in men (HR, 0.64; 95% CI, 0.42–0.98) but not women (HR, 1.34; 95% CI, 0.89–2.01; Pinteraction = 0.01). The observed inverse association between aspirin use and liver cancer in our study, together with previous data, suggests the merit of future intervention studies of aspirin and other agents that affect chronic inflammatory pathways for HCC and possibly ICC. Cancer Prev Res; 8(12); 1156–62. ©2015 AACR.
Causes of Death Following Transcatheter Aortic Valve Replacement: A Systematic Review and Meta‐Analysis
Authors: Xiong Tian‐Yuan , Liao Yan‐Biao , Zhao Zhen‐Gang , Xu Yuan‐Ning , Wei Xin , Zuo Zhi‐Liang , Li Yi‐Jian , Cao Jia‐Yu , Tang Hong , Jilaihawi Hasan , Feng Yuan , Chen Mao 
Published: September 2015

Background

Transcatheter aortic valve replacement (
TAVR
) is an effective alternative to surgical aortic valve replacement in patients at high surgical risk. However, there is little published literature on the exact causes of death.

Methods and Results

The PubMed database was systematically searched for studies reporting causes of death within and after 30 days following
TAVR
. Twenty‐eight studies out of 3934 results retrieved were identified. In the overall analysis, 46.4% and 51.6% of deaths were related to noncardiovascular causes within and after the first 30 days, respectively. Within 30 days of
TAVR
, infection/sepsis (18.5%), heart failure (14.7%), and multiorgan failure (13.2%) were the top 3 causes of death. Beyond 30 days, infection/sepsis (14.3%), heart failure (14.1%), and sudden death (10.8%) were the most common causes. All possible subgroup analyses were made. No significant differences were seen for proportions of cardiovascular deaths except the comparison between moderate (mean
STS
score 4 to 8) and high (mean
STS
score >8) ‐risk patients after 30 days post‐
TAVR
(56.0% versus 33.5%,
P
=0.005).

Conclusions

Cardiovascular and noncardiovascular causes of death are evenly balanced both in the perioperative period and at long‐term follow‐up after
TAVR
. Infection/sepsis and heart failure were the most frequent noncardiovascular and cardiovascular causes of death. This study highlights important areas of clinical focus that could further improve outcomes after
TAVR
.