bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effectiveness of Primary Anti-Aspergillus Prophylaxis during Remission Induction Chemotherapy of Acute Myeloid Leukemia
Authors: Gomes Marisa Z. R. , Jiang Ying , Mulanovich Victor E. , Lewis Russell E. , Kontoyiannis Dimitrios P. 
Published: March 2014

ABSTRACT

Although antifungal prophylaxis is frequently administered to patients with acute myeloid leukemia (AML) during remission-induction chemotherapy (RIC), its impact on reducing invasive fungal infections (IFIs) outside clinical trials is rarely reported. We performed a retrospective observational study to identify risk factors for development of IFIs (definite or probable, using revised European Organization for Research and Treatment of Cancer [EORTC] criteria) and all-cause mortality in a cohort of 152 AML patients receiving RIC (2009 to 2011). We also compared rates of IFI and mortality in patients who received echinocandin versus anti-
Aspergillus
azole (voriconazole or posaconazole) prophylaxis during the first 120 days of RIC. In multivariate analysis, clofarabine-based RIC (hazard ratio [HR], 3.5; 95% confidence interval [CI], 1.5 to 8.3;
P
= 0.004) and echinocandin prophylaxis (HR, 4.6; 95% CI, 1.8 to 11.9;
P
= 0.002) were independently associated with higher rates of IFI rates during RIC. Subsequent analysis failed to identify any malignancy- or chemotherapy-related covariates linked to echinocandin prophylaxis that accounted for the higher rates of breakthrough IFI. Although the possibility of other confounding variables cannot be excluded, our findings suggest that echinocandin-based prophylaxis during RIC for AML may be associated with a higher risk of breakthrough IFI.
Expression of the Effector Protein IncD in Chlamydia trachomatis Mediates Recruitment of the Lipid Transfer Protein CERT and the Endoplasmic Reticulum-Resident Protein VAPB to the Inclusion Membrane
Authors: Agaisse Hervé , Derré Isabelle 
Published: March 2014

ABSTRACT

Chlamydia trachomatis
is an obligate intracellular human pathogen responsible for ocular and genital infections. To establish its membrane-bound intracellular niche, the inclusion,
C. trachomatis
relies on a set of effector proteins that are injected into the host cells or inserted into the inclusion membrane. We previously proposed that insertion of the
C. trachomatis
effector protein IncD into the inclusion membrane contributes to the recruitment of the lipid transfer protein CERT to the inclusion. Due to the genetically intractable status of
C. trachomatis
at that time, this model of IncD-CERT interaction was inferred from ectopic expression of IncD and CERT in the host cell. In the present study, we investigated the impact of conditionally expressing a FLAG-tagged version of IncD in
C. trachomatis
. This genetic approach allowed us to establish that IncD-3×FLAG localized to the inclusion membrane and caused a massive recruitment of the lipid transfer protein CERT that relied on the PH domain of CERT. In addition, we showed that the massive IncD-dependent association of CERT with the inclusion led to an increased recruitment of the endoplasmic reticulum (ER)-resident protein VAPB, and we determined that, at the inclusion, CERT-VAPB interaction relied on the FFAT domain of CERT. Altogether, the data presented here show that expression of the
C. trachomatis
effector protein IncD mediates the recruitment of the lipid transfer protein CERT and the ER-resident protein VAPB to the inclusion.
Catheter-Associated Urinary Tract Infection by Pseudomonas aeruginosa Is Mediated by Exopolysaccharide-Independent Biofilms
Authors: Cole Stephanie J. , Records Angela R. , Orr Mona W. , Linden Sara B. , Lee Vincent T. 
Published: March 2014

ABSTRACTPseudomonas aeruginosais an opportunistic human pathogen that is especially adept at forming surface-associated biofilms.P. aeruginosacauses catheter-associated urinary tract infections (CAUTIs) through biofilm formation on the surface of indwelling catheters.P. aeruginosaencodes three extracellular polysaccharides, PEL, PSL, and alginate, and utilizes the PEL and PSL polysaccharides to form biofilmsin vitro; however, the requirement of these polysaccharides duringin vivoinfections is not well understood. Here we show in a murine model of CAUTI that PAO1, a strain harboringpel,psl, andalggenes, and PA14, a strain harboringpelandalggenes, form biofilms on the implanted catheters. To determine the requirement of exopolysaccharide duringin vivobiofilm infections, we tested isogenic mutants lacking thepel,psl, andalgoperons and showed that PA14 mutants lacking these operons can successfully form biofilms on catheters in the CAUTI model. To determine the host factor(s) that induces the ΔpelDmutant to form biofilm, we tested mouse, human, and artificial urine and show that urine can induce biofilm formation by the PA14 ΔpelDmutant. By testing the major constituents of urine, we show that urea can induce apel-,psl-, andalg-independent biofilm. Thesepel-,psl-, andalg-independent biofilms are mediated by the release of extracellular DNA. Treatment of biofilms formed in urea with DNase I reduced the biofilm, indicating that extracellular DNA supports biofilm formation. Our results indicate that the opportunistic pathogenP. aeruginosautilizes a distinct program to form biofilms that are independent of exopolysaccharides during CAUTI.
Development of an Aotus nancymaae Model for Shigella Vaccine Immunogenicity and Efficacy Studies
Authors: Gregory Michael , Kaminski Robert W. , Lugo-Roman Luis A. , Galvez Carrillo Hugo , Tilley Drake Hamilton , Baldeviano Christian , Simons Mark P. , Reynolds Nathanael D. , Ranallo Ryan T. , Suvarnapunya Akamol E. , Venkatesan Malabi M. , Oaks Edwin V. 
Published: March 2014

ABSTRACT

Several animal models exist to evaluate the immunogenicity and protective efficacy of candidate
Shigella
vaccines. The two most widely used nonprimate models for vaccine development include a murine pulmonary challenge model and a guinea pig keratoconjunctivitis model. Nonhuman primate models exhibit clinical features and gross and microscopic colonic lesions that mimic those induced in human shigellosis. Challenge models for enterotoxigenic
Escherichia coli
(ETEC) and
Campylobacter
spp. have been successfully developed with
Aotus nancymaae
, and the addition of a
Shigella-Aotus
challenge model would facilitate the testing of combination vaccines. A series of experiments were designed to identify the dose of
Shigella flexneri
2a strain 2457T that induces an attack rate of 75% in the
Aotus
monkey. After primary challenge, the dose required to induce an attack rate of 75% was calculated to be 1 × 10
11
CFU.
Shigella
-specific immune responses were low after primary challenge and subsequently boosted upon rechallenge. However, preexisting immunity derived from the primary challenge was insufficient to protect against the homologous
Shigella
serotype. A successive study in
A. nancymaae
evaluated the ability of multiple oral immunizations with live-attenuated
Shigella
vaccine strain SC602 to protect against challenge. After three oral immunizations, animals were challenged with
S. flexneri
2a 2457T. A 70% attack rate was demonstrated in control animals, whereas animals immunized with vaccine strain SC602 were protected from challenge (efficacy of 80%;
P
= 0.05). The overall study results indicate that the
Shigella-Aotus nancymaae
challenge model may be a valuable tool for evaluating vaccine efficacy and investigating immune correlates of protection.
Bacterial Genome Instability
Authors: Darmon Elise , Leach David R. F. 
Published: March 2014

SUMMARY
Bacterial genomes are remarkably stable from one generation to the next but are plastic on an evolutionary time scale, substantially shaped by horizontal gene transfer, genome rearrangement, and the activities of mobile DNA elements. This implies the existence of a delicate balance between the maintenance of genome stability and the tolerance of genome instability. In this review, we describe the specialized genetic elements and the endogenous processes that contribute to genome instability. We then discuss the consequences of genome instability at the physiological level, where cells have harnessed instability to mediate phase and antigenic variation, and at the evolutionary level, where horizontal gene transfer has played an important role. Indeed, this ability to share DNA sequences has played a major part in the evolution of life on Earth. The evolutionary plasticity of bacterial genomes, coupled with the vast numbers of bacteria on the planet, substantially limits our ability to control disease.
Utilization of Glyphosate as Phosphate Source: Biochemistry and Genetics of Bacterial Carbon-Phosphorus Lyase
Authors: Hove-Jensen Bjarne , Zechel David L. , Jochimsen Bjarne 
Published: March 2014

SUMMARY

After several decades of use of glyphosate, the active ingredient in weed killers such as Roundup, in fields, forests, and gardens, the biochemical pathway of transformation of glyphosate phosphorus to a useful phosphorus source for microorganisms has been disclosed. Glyphosate is a member of a large group of chemicals, phosphonic acids or phosphonates, which are characterized by a carbon-phosphorus bond. This is in contrast to the general phosphorus compounds utilized and metabolized by microorganisms. Here phosphorus is found as phosphoric acid or phosphate ion, phosphoric acid esters, or phosphoric acid anhydrides. The latter compounds contain phosphorus that is bound only to oxygen. Hydrolytic, oxidative, and radical-based mechanisms for carbon-phosphorus bond cleavage have been described. This review deals with the radical-based mechanism employed by the carbon-phosphorus lyase of the carbon-phosphorus lyase pathway, which involves reactions for activation of phosphonate, carbon-phosphorus bond cleavage, and further chemical transformation before a useful phosphate ion is generated in a series of seven or eight enzyme-catalyzed reactions. The
phn
genes, encoding the enzymes for this pathway, are widespread among bacterial species. The processes are described with emphasis on glyphosate as a substrate. Additionally, the catabolism of glyphosate is intimately connected with that of aminomethylphosphonate, which is also treated in this review. Results of physiological and genetic analyses are combined with those of bioinformatics analyses.
Carbohydrate Metabolism in Archaea: Current Insights into Unusual Enzymes and Pathways and Their Regulation
Authors: Bräsen Christopher , Esser Dominik , Rauch Bernadette , Siebers Bettina 
Published: March 2014

SUMMARYThe metabolism ofArchaea, the third domain of life, resembles in its complexity those ofBacteriaand lowerEukarya. However, this metabolic complexity inArchaeais accompanied by the absence of many “classical” pathways, particularly in central carbohydrate metabolism. Instead,Archaeaare characterized by the presence of unique, modified variants of classical pathways such as the Embden-Meyerhof-Parnas (EMP) pathway and the Entner-Doudoroff (ED) pathway. The pentose phosphate pathway is only partly present (if at all), and pentose degradation also significantly differs from that known for bacterial model organisms. These modifications are accompanied by the invention of “new,” unusual enzymes which cause fundamental consequences for the underlying regulatory principles, and classical allosteric regulation sites well established inBacteriaandEukaryaare lost. The aim of this review is to present the current understanding of central carbohydrate metabolic pathways and their regulation inArchaea. In order to give an overview of their complexity, pathway modifications are discussed with respect to unusual archaeal biocatalysts, their structural and mechanistic characteristics, and their regulatory properties in comparison to their classic counterparts fromBacteriaandEukarya. Furthermore, an overview focusing on hexose metabolic, i.e., glycolytic as well as gluconeogenic, pathways identified in archaeal model organisms is given. Their energy gain is discussed, and new insights into different levels of regulation that have been observed so far, including the transcript and protein levels (e.g., gene regulation, known transcription regulators, and posttranslational modification via reversible protein phosphorylation), are presented.
Nitrofurantoin immune-mediated drug-induced liver injury: a serious complication of a commonly prescribed medication
Authors: Hydes Theresa , Wright Mark , Jaynes Eleanor , Nash Kathryn 
Published: March 2014

SummaryNitrofurantoin is recommended for first line prophylaxis of recurrent urinary tract infections. Despite a number of side effects it is increasingly prescribed due to its high efficacy, low cost and minimal antimicrobial resistance. Nitrofurantoin-induced immune-mediated liver injury is a particularly serious complication, resulting in both acute hepatic failure and cirrhosis with continued use. We describe the course of two patients who recently presented to our hospital in order to highlight this.
Longitudinal assessment of chlorpyrifos exposure and self-reported neurological symptoms in adolescent pesticide applicators
Authors: Khan Khalid , Ismail Ahmed A , Abdel Rasoul Gaafar , Bonner Matthew R , Lasarev Michael R , Hendy Olfat , Al-Batanony Manal , Crane Alice L , Singleton Steven T , Olson James R , Rohlman Diane S 
Published: March 2014

ObjectivesOccupational exposure of organophosphorus pesticides, such as chlorpyrifos (CPF), in adolescents is of particular concern because of the potential vulnerability of the developing neurological system. The objectives of this study were to examine how neurological symptoms reported over the application season vary across time, whether these effects are reversible postapplication and if there are associations between CPF biomarkers and neurological symptoms in an adolescent study population.SettingThe longitudinal study was conducted in two agricultural districts of Menoufia Governorate, Egypt between April 2010 and January 2011.ParticipantsMale adolescent participants, including CPF applicators (n=57) and non-applicators (n=38), were recruited.Primary and secondary outcome measuresSelf-reported data for 25 neurological symptoms were collected at 32 time points over the 8-month period before, during and after the application season. Additionally, urine and blood samples were collected to measure urine trichloro-2-pyridinol (TCPy), a CPF-specific biomarker and blood cholinesterase activity.ResultsApplicators and non-applicators report the highest numbers of symptoms during the application season, followed by a reduction in symptoms after the application ended. Applicators reported a greater percentage of neurological symptoms, relative to baseline, than non-applicators after accounting for potential covariates. Among the applicators, cumulative TCPy was positively and significantly associated with the average percentage of symptoms (B=4.56, 95% CI 3.29 to 5.84; p<0.001). Significant associations (p=0.03–0.07) between the change in butyrylcholinesterase activity from the preapplication to the postapplication season and several domains of neurological symptoms were also found, even after adjusting for potential covariates.ConclusionsThese observations demonstrate changes in the reporting of symptoms across the application season, showing an increase in symptom reporting during application and recovery following the end of pesticide application. These findings reinforce the growing concern regarding the neurotoxic health effects of CPF in adolescent applicators in developing countries and the need for developing and implementing intervention programmes.
Management of urinary tract infections in elderly patients: Strategies for improvement
Authors: Lim Vee Han , Whitehurst Thomas , Usoro Emem , Ming Ng Sieu 
Published: March 2014

AbstractUrinary tract infection (UTI) is one of the most common infections affecting the elderly. However, UTI is overdiagnosed and overtreated in this group. This project aimed to look into strategies for improving the management of UTI in elderly medical inpatients. A retrospective audit was performed on the case notes of medical inpatients in a district general hospital from December 2012 to April 2013. The target measures for improvement include increasing adherence to SIGN guidelines in the diagnosis of UTI, increasing the frequency and timeliness of urinary culture collection in suspected UTI, and increasing use of urine culture sensitivities to tailor antimicrobial treatments.Initial baseline measurement revealed 16 patients treated for UTI. 31.3% of these fulfilled SIGN criteria for UTI. 68.5% had urine cultures performed. 60% of patients with positive urine cultures had correct antibiotic therapy after sensitivity results. The mean time from the diagnosis of UTI to urine collection for culture was 4 days.Three further cycles were performed. Following each cycle, improvement measures were implemented to raise the awareness of medical staff about the management of UTI in the elderly. These comprised presentations to junior doctors at local teaching sessions; emails to ward managers with results of the previous audit cycle broken down by ward; and prominent display of guidelines on medical wards and ensuring availability of ‘Newcastle pads’ for taking sterile urine cultures from incontinent patients.In the final cycle, 19 patients were diagnosed with UTI. 42.1% of these fulfilled SIGN criteria for diagnosis of UTI. 89.5% had urine cultures sent. 86.7% of patients with a positive urine culture were treated with appropriate antibiotics after sensitivities became available. Mean time from UTI diagnosis to culture collection improved to zero days.In conclusion, continuous educational measures, performance feedback, and increased availability of specialist equipment are imperative for improving management of UTIs in the elderly.
The value of autopsies in the era of high-tech medicine: discrepant findings persist
Authors: Kuijpers Chantal C H J , Fronczek Judith , van de Goot Frank R W , Niessen Hans W M , van Diest Paul J , Jiwa Mehdi 
Published: March 2014

AimsAlthough the autopsy is still the gold standard for quality assessment of clinical diagnoses, autopsy rates have been declining over the last decades to <10%. The aim of this study was to investigate the value of autopsies in the high-tech medicine era by determining the frequency of discrepancies between clinical and autopsy diagnoses.MethodsWe classified all adult autopsy cases (n=460), performed at Symbiant, Pathology Expert Centre, in 2007 and 2012/2013, as having major, or minor discrepancy or total concordance. The roles of possible contributory factors were analysed. Finally, we assessed the role of microscopic examination in identifying cause of death.ResultsMajor and minor discrepancies were found in 23.5% and 32.6% of the classifiable autopsies, respectively. Most commonly observed major discrepancies were myocardial infarction, pulmonary embolism and pneumonia. Improper imaging and discontinuation of active treatment were significantly associated with a higher and a lower frequency of major discrepancies, respectively. Comparing 2007 and 2012/2013, the frequency of minor discrepancies significantly increased from 26.8% to 39.3%. Final admission length of >2 days was significantly associated with a lower frequency of class III minor discrepancies. Microscopic examination contributed to establishing cause of death in 19.6% of the cases.ConclusionsDiscrepant findings persist at autopsy, even in the era of high-tech medicine. Therefore, autopsies still should serve as a very important part of quality control in clinical diagnosis and treatment. Learning from individual and system-related diagnostic errors can aid in improving patient safety.
Fasting increases serum bilirubin levels in clinically normal, healthy males but not females: a retrospective study from phase I clinical trial participants
Authors: Griffin Paul M , Elliott Suzanne L , Manton Kerry J 
Published: March 2014

AimTo examine if fasting affects serum bilirubin levels in clinically healthy males and females.MethodsWe used retrospective data from phase I clinical trials where blood was collected in either a fed or fasting state at screening and predosing time points and analysed for total bilirubin levels as per standard clinical procedures. Participants were clinically healthy males (n=105) or females (n=30) aged 18–48 inclusive who participated in a phase I clinical trial in 2012 or 2013.ResultsWe found a statistically significant increase in total serum bilirubin levels in fasting males as compared with non-fasting males. The fasting time correlated positively with increased bilirubin levels. The age of the healthy males did not correlate with their fasting bilirubin level. We found no correlation between fasting and bilirubin levels in clinically normal females.ConclusionsThe recruitment and screening of volunteers for a clinical trial is a time-consuming and expensive process. This study clearly demonstrates that testing for serum bilirubin should be conducted on non-fasting male subjects. If fasting is required, then participants should not be excluded from a trial based on an elevated serum bilirubin that is deemed non-clinically significant.
Influence of igneous sills on Paleocene turbidite deposition in the Faroe–Shetland Basin: a case study in Flett and Muckle sub-basin and its implication for hydrocarbon exploration
Authors: Egbeni Sylvester , McClay Ken , Jian-kui Fu Jack , Bruce Duncan 
Published: March 2014

Abstract
A new interpretation on three-dimensional seismic data from the Flett and Muckle sub-basins of the Faroe–Shetland Basin has shown dyke and sill emplacement influencing the Paleocene turbidite deposition. Sill and dyke emplacement in the study area created significant inflation anticlines during Paleocene time and affected palaeotopography at the seafloor. The uplift of older Early Paleocene (Sullom) and Middle Paleocene (early Vaila) turbidite deposits results in their erosion and redeposition in adjacent lows or transports them further into the basin by erosive channels. By using public domain well and biostratigraphic data from wells 208/19-1, 206/2a-1 and 206/1-2, seismic data and the use of seismic sequence stratigraphy to map the onlapping seismic reflectors on the flanks of the inflated anticlines, the relative timing of sill emplacement in the study area is shown to be Early–Middle Paleocene. The ability to identify these systems and understand the interaction between palaeotopography and Paleocene turbidite deposition in the basin is key to unlocking the hydrocarbon potential in the UK flank of the Faroe–Shetland Basin.
Faroe Marine Ash Zone IV: a new MIS 3 ash zone on the Faroe Islands margin
Authors: Wastegård Stefan , Rasmussen Tine L. 
Published: March 2014

Abstract
A basaltic tephra layer from MIS 3 has been discovered by analysis of cores from the Faroe Islands margin. The tephra layer appears up to 20 cm thick in some records. After the first main fall-out event the tephra is believed to be mainly deposited and redistributed by bottom currents. Geochemical analyses suggest that the tephra is relatively undisturbed by allochtonous tephra grains and unmixed. The peak occurrences are in the lower part of GIS (Greenland Interstadial) 12 and we suggest naming this new tephra Faroe Marine Ash Zone IV (FMAZ IV), following the nomenclature adopted for previous ash zones found on the Faroe Islands margin. Geochemical analyses of the tephra show affinities with the Grímsvötn volcanic system in the Eastern Volcanic Zone in south Iceland. The average age of FMAZ IV from four independent age models is 46 800±1000 years BP. We suggest that the V5 ash zone, found on the Reykjanes Ridge is a correlative to the FMAZ IV.

Supplementary material:

Single-grain analyses of tephra from FMAZ IV in cores from the northern Faroe margin and the central Faroe-Shetland Channel are available at
http://www.geolsoc.org.uk/SUP18714