bluuebunny/crossref_metadata_2025_split huggingface dataset:
Emerging Fungal Pathogen Candida auris Evades Neutrophil Attack
Authors: Johnson Chad J. , Davis J. Muse , Huttenlocher Anna , Kernien John F. , Nett Jeniel E. 
Published: August 2018

ABSTRACT

Candida auris
has recently emerged as the first fungal pathogen to cause a global public health threat. The reason this species is causing hospital-associated outbreaks of invasive candidiasis with high mortality is unknown. In this study, we examine the interaction of
C. auris
with neutrophils, leukocytes critical for control of invasive fungal infections. We show that human neutrophils do not effectively kill
C. auris
. Compared to
Candida albicans
, neutrophils poorly recruited to
C. auris
and failed to form neutrophil extracellular traps (NETs), which are structures of DNA, histones, and proteins with antimicrobial activity. In mixed cultures, neutrophils preferentially engaged and killed
C. albicans
over
C. auris
. Imaging of neutrophils in a zebrafish larval model of invasive candidiasis revealed the recruitment of approximately 50% fewer neutrophils in response to
C. auris
compared to
C. albicans
. Upon encounter with
C. albicans
in the zebrafish hindbrain, neutrophils produced clouds of histones, suggesting the formation of NETs. These structures were not observed in
C. auris
infection. Evasion of neutrophil attack and innate immunity offers an explanation for the virulence of this pathogen.

IMPORTANCE
The emerging fungal pathogen
Candida auris
has produced numerous outbreaks of invasive disease in hospitals worldwide. Why this species causes deadly disease is unknown. Our findings reveal a failure of neutrophils to kill
C. auris
compared to the most commonly encountered
Candida
species,
C. albicans
. While neutrophils produce neutrophil extracellular traps (NETs) upon encounter with
C. albicans
, these antimicrobial structures are not formed in response to
C. auris
. Using human neutrophils and a zebrafish model of invasive candidiasis, we show that
C. auris
poorly recruits neutrophils and evades immune attack. Identification of this impaired innate immune response to
C. auris
sheds light on the dismal outcomes for patients with invasive disease.
Discovery of New Genes Involved in Curli Production by a Uropathogenic Escherichia coli Strain from the Highly Virulent O45:K1:H7 Lineage
Authors: Nhu Nguyen Thi Khanh , Phan Minh-Duy , Peters Kate M. , Lo Alvin W. , Forde Brian M. , Min Chong Teik , Yin Wai-Fong , Chan Kok-Gan , Chromek Milan , Brauner Annelie , Chapman Matthew R. , Beatson Scott A. , Schembri Mark A. 
Published: August 2018

ABSTRACT

Curli are bacterial surface-associated amyloid fibers that bind to the dye Congo red (CR) and facilitate uropathogenic
Escherichia coli
(UPEC) biofilm formation and protection against host innate defenses. Here we sequenced the genome of the curli-producing UPEC pyelonephritis strain MS7163 and showed it belongs to the highly virulent O45:K1:H7 neonatal meningitis-associated clone. MS7163 produced curli at human physiological temperature, and this correlated with biofilm growth, resistance of sessile cells to the human cationic peptide cathelicidin, and enhanced colonization of the mouse bladder. We devised a forward genetic screen using CR staining as a proxy for curli production and identified 41 genes that were required for optimal CR binding, of which 19 genes were essential for curli synthesis. Ten of these genes were novel or poorly characterized with respect to curli synthesis and included genes involved in purine
de novo
biosynthesis, a regulator that controls the Rcs phosphorelay system, and a novel repressor of curli production (referred to as
rcpA
). The involvement of these genes in curli production was confirmed by the construction of defined mutants and their complementation. The mutants did not express the curli major subunit CsgA and failed to produce curli based on CR binding. Mutation of
purF
(the first gene in the purine biosynthesis pathway) and
rcpA
also led to attenuated colonization of the mouse bladder. Overall, this work has provided new insight into the regulation of curli and the role of these amyloid fibers in UPEC biofilm formation and pathogenesis.

IMPORTANCE
Uropathogenic
Escherichia coli
(UPEC) strains are the most common cause of urinary tract infection, a disease increasingly associated with escalating antibiotic resistance. UPEC strains possess multiple surface-associated factors that enable their colonization of the urinary tract, including fimbriae, curli, and autotransporters. Curli are extracellular amyloid fibers that enhance UPEC virulence and promote biofilm formation. Here we examined the function and regulation of curli in a UPEC pyelonephritis strain belonging to the highly virulent O45:K1:H7 neonatal meningitis-associated clone. Curli expression at human physiological temperature led to increased biofilm formation, resistance of sessile cells to the human cationic peptide LL-37, and enhanced bladder colonization. Using a comprehensive genetic screen, we identified multiple genes involved in curli production, including several that were novel or poorly characterized with respect to curli synthesis. In total, this study demonstrates an important role for curli as a UPEC virulence factor that promotes biofilm formation, resistance, and pathogenesis.
Genomic Characterization and Copy Number Variation of
Bacillus anthracis
Plasmids pXO1 and pXO2 in a Historical Collection of 412 Strains
Authors: Pena-Gonzalez Angela , Rodriguez-R Luis M. , Marston Chung K. , Gee Jay E. , Gulvik Christopher A. , Kolton Cari B. , Saile Elke , Frace Michael , Hoffmaster Alex R. , Konstantinidis Konstantinos T. 
Published: August 2018

Bacillus anthracis
microorganisms are of historical and epidemiological importance and are among the most homogenous bacterial groups known, even though the
B. anthracis
genome is rich in mobile elements. Mobile elements can trigger the diversification of lineages; therefore, characterizing the extent of genomic variation in a large collection of strains is critical for a complete understanding of the diversity and evolution of the species. Here, we sequenced a large collection of
B. anthracis
strains (>400) that were recovered from human, animal, and environmental sources around the world. Our results confirmed the remarkable stability of gene content and synteny of the anthrax plasmids and revealed no signal of plasmid exchange between
B. anthracis
and pathogenic
B. cereus
isolates but rather predominantly vertical descent. These findings advance our understanding of the biology and pathogenomic evolution of
B. anthracis
and its plasmids.
A randomised placebo-controlled double-blind trial to assess the safety of intramuscular administration of allogeneic mesenchymal stromal cells for digital ulcers in systemic sclerosis: the MANUS Trial protocol
Authors: van Rhijn-Brouwer Femke C C , Gremmels Hendrik , Fledderus Joost O , Schuurman Arnold H , Bonte-Mineur Femke , Vonk Madelon C , Voskuyl Alexandre E , de Vries-Bouwstra Jeska K , Coert J Henk , Radstake Timothy R D J , van Laar Jacob M , Verhaar Marianne C 
Published: August 2018

IntroductionSystemic sclerosis (SSc) is an autoimmune disease characterised by inflammation, fibrosis and vasculopathy. Digital ulcers (DUs) are a frequent manifestation of vasculopathy in patients with SSc. Despite recent advances in pharmacological treatments, DU still have major health and economic implications. As there is currently no proven therapeutic strategy to promote DU healing, new treatments are urgently needed. Mesenchymal stem or stromal cells (MSCs) may provide a novel therapy for DU in SSc, because of their immunomodulatory and vasculoregenerative properties. Allogeneic MSC therapy involves functionally competent MSCs from healthy donors and may be used as ‘off-the-shelf’ available treatment. This study will evaluate whether allogeneic MSC therapy is a safe and potentially efficacious treatment for DU of SSc.Methods and analysisThe MANUS (Mesenchymal stromal cells forAngiogenesis andNeovascularization in digitalUlcers ofSystemic Sclerosis) Trial is a double-blind randomised placebo-controlled trial. 20 patients with SSc with refractory DU will be randomised to receive eight intramuscular injections with either placebo or 50*106MSCs. The primary outcome is the toxicity of the treatment at 12 weeks after administration. Secondary outcomes include (serious) adverse events, number and time to healing of DU, pain, reported hand function, quality of life and SSc disease activity. We will also evaluate changes in nailfold capillaroscopy pattern, as well as biochemical parameters and biomarkers in peripheral blood and skin biopsies. Follow-up visits will be scheduled at 48 hours and 2, 4, 8, 12, 24 and 52 weeks post-treatment. If the results confirm safety, feasibility and potential efficacy, a large multicentre randomised controlled trial with longer follow-up will be initiated focusing on efficacy.Ethics and disseminationThe study has been approved by the Dutch Central Committee on Research Concerning Human Subjects (protocol no: NL51705.000.15). The results will be disseminated through patient associations and conventional scientific channels.Trial registration numberNCT03211793; Pre-results.
Comparative morbidities and the share of emergencies in hospital admissions in deprived areas: a method and evidence from English administrative data
Authors: McCormick Barry , Hill Peter-Sam , Redding Stuart 
Published: August 2018

ObjectiveVarious studies find that the share of emergencies in hospital admissions is higher in deprived areas, but both the explanation and policy implications are unclear. We estimate the extent to which this finding is due to a different disease mix in deprived areas, rather than other explanations such as patient behaviour and general practitioner effectiveness.DesignSecondary analysis using English Hospital Episode Statistics data, with disease for elective and emergency admissions in 2008/2009 coded at 186 blocks or 1230 categories and aggregated to lower layer super output area of residence. It is then linked to an appropriate measure of deprivation.Outcome measuresThe difference in the share of emergencies in hospital admissions between communities in the highest and lowest deciles of deprivation; and the percentage of this difference that is explained if areas in the least deprived decile have the same disease mix as those in the most deprived decile.ResultsUsing the finest disease classification scheme (1230 categories), 71% of the higher share of admissions that were emergencies in decile 1 areas relative to decile 10, is explained by the “adverse” case mix (CM) in deprived areas. The remainder reflects the higher relative use of emergency care in deprived areas for the same conditions. Higher incidence of respiratory and circulatory diseases in deprived areas explains about 30% of the CM contribution. Diseases of the digestive system and abdomen have a high relative use of emergency care in deprived areas.ConclusionsThe higher use of emergency care in deprived areas is primarily a symptom of the higher prevalence of diseases which have high national rates of emergency to elective care—especially respiratory diseases—rather than an indication of less effective primary care. Nevertheless, there is a higher share of emergency care in admissions in deprived areas for several diseases, most notably of the digestive system.
Gout and hearing impairment in the elderly: a retrospective cohort study using the US Medicare claims data
Authors: Singh Jasvinder A , Cleveland John D 
Published: August 2018

ObjectivesTo evaluate whether gout is associated with a higher risk of hearing loss in older adults.DesignRetrospective cohort study.SettingUSA.Participants5% random sample of US Medicare claims 2006–2012, representative of US adults aged 65 years or older.Primary and secondary outcomesIncident (new) hearing loss identified by the presence of at least two claims at least 4 weeks apart with an International Classification of Diseases, Ninth Revision, 389.xx, with no respective claim in the baseline 1-year observation period.ResultsAmong the 1.71 million eligible people, 89 409 developed incident hearing impairment. The crude incidence rates of incident hearing impairment in people with versus without gout were 16.9 vs. 8.7 per 1000 person-years. Using Cox regression analyses adjusted for demographics, medical comorbidity and common cardiovascular and gout medications, we found that gout was associated with a significantly higher HR of incident hearing impairment, HR was 1.44 (95% CI 1.40 to 1.49, p<0.0001). Findings were confirmed in sensitivity analyses that substituted continuous Charlson-Romano Index with categorical variable or all comorbidities and additionally cardiovascular risk factors, with minimal attenuation of HR.ConclusionsGout is associated with a higher risk of development of hearing loss in older adults. Future studies need to assess the underlying mechanisms of this association.
Short-term outcomes after emergency surgery for complicated peptic ulcer disease from the UK National Emergency Laparotomy Audit: a cohort study
Authors: Byrne Benjamin E , Bassett Michael , Rogers Chris A , Anderson Iain D , Beckingham Ian , Blazeby Jane M 
Published: August 2018

ObjectivesThis study used national audit data to describe current management and outcomes of patients undergoing surgery for complications of peptic ulcer disease (PUD), including perforation and bleeding. It was also planned to explore factors associated with fatal outcome after surgery for perforated ulcers. These analyses were designed to provide a thorough understanding of current practice and identify potentially modifiable factors associated with outcome as targets for future quality improvement.DesignNational cohort study using National Emergency Laparotomy Audit (NELA) data.SettingEnglish and Welsh hospitals within the National Health Service.ParticipantsAdult patients admitted as an emergency with perforated or bleeding PUD between December 2013 and November 2015.InterventionsLaparotomy for bleeding or perforated peptic ulcer.Primary and secondary outcome measuresThe primary outcome was 60-day in-hospital mortality. Secondary outcomes included length of postoperative stay, readmission and reoperation rate.Results2444 and 382 procedures were performed for perforated and bleeding ulcers, respectively. In-hospital 60-day mortality rates were 287/2444 (11.7%, 95% CI 10.5% to 13.1%) for perforations, and 68/382 (17.8%, 95% CI 14.1% to 22.0%) for bleeding. Median (IQR) 2-year institutional volume was 12 (7–17) and 2 (1–3) for perforation and bleeding, respectively. In the exploratory analysis, age, American Society of Anesthesiology score and preoperative systolic blood pressure were associated with mortality, with no association with time from admission to operation, surgeon grade or operative approach.ConclusionsPatients undergoing surgery for complicated PUD face a high 60-day mortality risk. Exploratory analyses suggested fatal outcome was primarily associated with patient rather than provider care factors. Therefore, it may be challenging to reduce mortality rates further. NELA data provide important benchmarking for patient consent and has highlighted low institutional volume and high mortality rates after surgery for bleeding peptic ulcers as a target for future research and improvement.
Accuracy of NEXUS II head injury decision rule in children: a prospective PREDICT cohort study
Authors: Babl Franz E , Oakley Ed , Dalziel Stuart R , Borland Meredith L , Phillips Natalie , Kochar Amit , Dalton Sarah , Cheek John Alexander , Gilhotra Yuri , Furyk Jeremy , Neutze Jocelyn , Donath Susan , Hearps Stephen , Crowe Louise M , Arpone Marta , Bressan Silvia , Lyttle Mark D 
Published: August 2018

ObjectiveThe National Emergency X-Radiography Utilisation Study II (NEXUS II) clinical decision rule (CDR) can be used to optimise the use of CT in children with head trauma. We set out to externally validate this CDR in a large cohort.MethodsWe performed a prospective observational study of patients aged <18 years presenting with head trauma of any severity to 10 Australian/New Zealand EDs. In a planned secondary analysis, we assessed the accuracy of the NEXUS II CDR (with 95% CI) to detect clinically important intracranial injury (ICI). We also assessed clinician accuracy without the rule.ResultsOf 20 137 total patients, we excluded 28 with suspected penetrating injury. Median age was 4.2 years. CTs were obtained in ED for 1962 (9.8%), of whom 377 (19.2%) had ICI as defined by NEXUS II. 74 (19.6% of ICI) patients underwent neurosurgery.Sensitivity for ICI based on the NEXUS II CDR was 379/383 (99.0 (95% CI 97.3% to 99.7%)) and specificity was 9320/19 726 (47.2% (95% CI 46.5% to 47.9%)) for the total cohort. Sensitivity in the CT-only cohort was similar. Of the 18 022 children without CT in ED, 49.4% had at least one NEXUS II risk criterion. Sensitivity for ICI by the clinicians without the rule was 377/377 (100.0% (95% CI 99.0% to 100.0%)) and specificity was 18 147/19 732 (92.0% (95% CI 91.6% to 92.3%)).ConclusionsNEXUS II had high sensitivity, similar to the derivation study. However, approximately half of unimaged patients were positive for NEXUS II risk criteria; this may result in an increased CT rate in a setting with high clinician accuracy.
Effects of office workstation type on physical activity and stress
Authors: Lindberg Casey M , Srinivasan Karthik , Gilligan Brian , Razjouyan Javad , Lee Hyoki , Najafi Bijan , Canada Kelli J , Mehl Matthias R , Currim Faiz , Ram Sudha , Lunden Melissa M , Heerwagen Judith H , Kampschroer Kevin , Sternberg Esther M 
Published: August 2018

ObjectiveOffice environments have been causally linked to workplace-related illnesses and stress, yet little is known about how office workstation type is linked to objective metrics of physical activity and stress. We aimed to explore these associations among office workers in US federal office buildings.MethodsWe conducted a wearable, sensor-based, observational study of 231 workers in four office buildings. Outcome variables included workers’ physiological stress response, physical activity and perceived stress. Relationships between office workstation type and these variables were assessed using structural equation modelling.ResultsWorkers in open bench seating were more active at the office than those in private offices and cubicles (open bench seating vs private office=225.52 mG (31.83% higher on average) (95% CI 136.57 to 314.46); open bench seating vs cubicle=185.13 mG (20.16% higher on average) (95% CI 66.53 to 303.72)). Furthermore, workers in open bench seating experienced lower perceived stress at the office than those in cubicles (−0.27 (9.10% lower on average) (95% CI −0.54 to −0.02)). Finally, higher physical activity at the office was related to lower physiological stress (higher heart rate variability in the time domain) outside the office (−26.12 ms/mG (14.18% higher on average) (95% CI −40.48 to −4.16)).ConclusionsOffice workstation type was related to enhanced physical activity and reduced physiological and perceived stress. This research highlights how office design, driven by office workstation type, could be a health-promoting factor.
Heparin-induced thrombocytopaenia
Authors: Prince Mark , Wenham Tim 
Published: August 2018

AbstractHeparin-induced thrombocytopaenia (HIT) is a severe and potentially life-threatening adverse drug reaction. Patients become extremely hypercoagulable, and this can lead to life-threatening and limb-threatening thrombosis with a mortality of 5%–10%. HIT is an antibody-mediated process in which platelet activation occurs. Diagnosis requires a high index of suspicion along with a scoring system and laboratory testing. Patients suspected of having HIT must not receive any further heparin or low-molecular weight heparin and must be started on an alternative anticoagulant such as argatroban or danaparoid. Fondaparinux may also be considered but is not licenced for this indication.
Bridging the HIV-syphilis testing gap: dual testing among men who have sex with men living in China
Authors: Ong Jason J , Liao Meizhen , Lee Amy , Fu Hongyun , Pan Stephen W , Tang Weiming , Wei Chongyi , Dan Wu , Yang Bin , Yang Ligang , Wang Cheng , Tucker Joseph D 
Published: August 2018

ObjectivesThe WHO recommends dual testing for HIV and syphilis among key populations, including men who have sex with men (MSM). We assessed the proportion of men who had dual tested and reasons for not dual testing.MethodsIn 2017, an online survey of MSM was conducted in eight cities from two provinces in China. Data on sociodemographics and sexual behaviours were collected. Descriptive analysis was used to examine the experience of dual testing. Multivariable logistic regression identified characteristics associated with men who had dual tested.ResultsAmong 802 men who had ever tested for HIV, 297 dual tested (37%, 95% CI 34 to 40). Men dual tested in a variety of settings: public hospital (35%), voluntary counselling and testing sites (28%), self-testing at home (18%), community-based organisation (8%), community health centre (7%), other (3%) or private hospital (1%). Greater odds for dual testing was found in men who had disclosed their sexuality to a healthcare provider (adjusted OR (AOR) 1.81, 95% CI 1.27 to 2.59, p=0.001), and who had substantial (AOR 2.71, 95% CI 1.67 to 4.41, p<0.001) or moderate community engagement in sexual health (AOR 2.30, 95% CI 1.49 to 3.57, p<0.001), compared with those with no community engagement. The most common reasons for not dual testing were no knowledge that they could be dual tested (34%), did not ask the doctor to be dual tested (25%) and did not believe they were at risk for syphilis (19%).ConclusionsChinese MSM are dual testing through a variety of test sites, including home self-testing. However, the overall dual testing rate remains low despite recent efforts to integrate HIV and syphilis testing.
Oxygen penetration and mineral stability within the San Manuel tailings, AZ
Authors: Declercq J. , Bowell R. J. 
Published: August 2018

Environmental impact assessment of tailings storage facilities focuses on defining the reactivity and potential for acid rock drainage and metal leaching (ARDML) through geochemical testing of representative samples and numerical predictive calculations. The acid generation potential of tailings is dependent on the reactivity of their sulphide content which is directly proportional to the oxygen concentration within the material. As such, predicting the oxygen concentration as a function of time and depth is critical to understand the acid generation potential of tailings material.
The aim of this study was to predict the oxygen flux and concentration as a function of time and depth within the San Manuel flotation copper tailings in Arizona, USA. This flow was combined with mineralogical data, including the presence of encapsulated sulphide, oxygen and moisture content to model oxidation and metal release in the tailings.
Numerical simulations, using reactive transport code MIN3P, correctly reproduced the San Manuel field and analytical results when the sulphide reactivity was controlled by reducing the effective sulphide mass within the numerical models from total sulphide to available sulphide. These calculations effectively demonstrated that an effective control minimizing sulphide oxidation exists within a portion of the San Manuel tailings.