bluuebunny/crossref_metadata_2025_split huggingface dataset:
Processing of
Candida albicans
Ece1p Is Critical for Candidalysin Maturation and Fungal Virulence
Authors: Richardson Jonathan P. , Mogavero Selene , Moyes David L. , Blagojevic Mariana , Krüger Thomas , Verma Akash H. , Coleman Bianca M. , De La Cruz Diaz Jacinto , Schulz Daniela , Ponde Nicole O. , Carrano Giulia , Kniemeyer Olaf , Wilson Duncan , Bader Oliver , Enoiu Simona I. , Ho Jemima , Kichik Nessim , Gaffen Sarah L. , Hube Bernhard , Naglik Julian R. 
Published: January 2018

ABSTRACT

Candida albicans
is an opportunistic fungal pathogen responsible for superficial and life-threatening infections in humans. During mucosal infection,
C. albicans
undergoes a morphological transition from yeast to invasive filamentous hyphae that secrete candidalysin, a 31-amino-acid peptide toxin required for virulence. Candidalysin damages epithelial cell plasma membranes and stimulates the activating protein 1 (AP-1) transcription factor c-Fos (via p38–mitogen-activated protein kinase [MAPK]), and the MAPK phosphatase MKP1 (via extracellular signal-regulated kinases 1 and 2 [ERK1/2]–MAPK), which trigger and regulate proinflammatory cytokine responses, respectively. The candidalysin toxin resides as a discrete cryptic sequence within a larger 271-amino-acid parental preproprotein, Ece1p. Here, we demonstrate that kexin-like proteinases, but not secreted aspartyl proteinases, initiate a two-step posttranslational processing of Ece1p to produce candidalysin. Kex2p-mediated proteolysis of Ece1p after Arg61 and Arg93, but not after other processing sites within Ece1p, is required to generate immature candidalysin from Ece1p, followed by Kex1p-mediated removal of a carboxyl arginine residue to generate mature candidalysin.
C. albicans
strains harboring mutations of Arg61 and/or Arg93 did not secrete candidalysin, were unable to induce epithelial damage and inflammatory responses
in vitro
, and showed attenuated virulence
in vivo
in a murine model of oropharyngeal candidiasis. These observations identify enzymatic processing of
C. albicans
Ece1p by kexin-like proteinases as crucial steps required for candidalysin production and fungal pathogenicity.

IMPORTANCE
Candida albicans
is an opportunistic fungal pathogen that causes mucosal infection in millions of individuals worldwide. Successful infection requires the secretion of candidalysin, the first cytolytic peptide toxin identified in any human fungal pathogen. Candidalysin is derived from its parent protein Ece1p. Here, we identify two key amino acids within Ece1p vital for processing and production of candidalysin. Mutations of these residues render
C. albicans
incapable of causing epithelial damage and markedly reduce mucosal infection
in vivo
. Importantly, candidalysin production requires two individual enzymatic events. The first involves processing of Ece1p by Kex2p, yielding immature candidalysin, which is then further processed by Kex1p to produce the mature toxin. These observations identify important steps for
C. albicans
pathogenicity at mucosal surfaces.
Retrospective analysis assessing the spatial and temporal distribution of paediatric acute respiratory tract infections in Ho Chi Minh City, Vietnam
Authors: Ho Nhan Thi , Thompson Corinne , Nhan Le Nguyen Thanh , Van Hoang Minh Tu , Dung Nguyen Thanh , Tran My Phuc , Quang Vo Minh , Minh Ngo Ngoc Quang , Tuan Tran Anh , Hung Nguyen Thanh , Tuan Ha Manh , Vinh Chau Nguyen Van , Wolbers Marcel , Thwaites Guy E , Choisy Marc , Baker Stephen 
Published: January 2018

BackgroundAcute respiratory tract infections (ARIs) are the leading cause of morbidity and mortality in young children in low/middle-income countries. Using routine hospital data, we aimed to examine the spatial distribution, temporal trends and climatic risk factors of paediatric ARIs in Vietnam.MethodsData from hospitalised paediatric (<16 years) patients with ARIs residing in Ho Chi Minh City (HCMC) between 2005 and 2010 were retrieved from the two main Children’s Hospitals and the Hospital for Tropical Diseases in HCMC. Spatial mapping and time series analysis were performed after disaggregating data into upper respiratory tract infections (URIs) and lower respiratory tract infections (LRIs).ResultsOver the study period, there were 155 999 paediatric patients admitted with ARIs (33% of all hospital admissions). There were 68 120 URIs (14%) and 87 879 LRIs (19%). The most common diagnoses were acute pharyngitis (28% of all ARI), pneumonia (21%), bronchitis (18%) and bronchiolitis (16%). A significant increasing trend over time was found for both URIs (mean weekly incidence per 1000 population, I=3.12), incidence rate ratio for 1-week increase in time (RR 1.0, 95% CI 1.02 to 1.17) for URI and (I=4.02, RR 1.08 (95% CI 1.006 to 1.16)) for LRI. The weekly URI incidence peaked in May–June and was significantly associated with lags in weekly URI incidence and the average humidity, rainfall and water level. The weekly LRI incidence exhibited significant seasonality (P<0.0001), with an annual peak in September–October and was significantly associated with lags in weekly LRI incidence and lags in weekly average temperature, rainfall and water level.ConclusionsARIs are a leading cause of childhood hospitalisation in HCMC, Vietnam. The incidence of ARIs was higher in the wet season and in specific HCMC districts. These results may guide health authorities in where and when to effectively allocate resources for the prevention and control of ARIs.
Small cortical grey matter lesions show no persistent infarction in transient ischaemic attack? A prospective cohort study
Authors: Havsteen Inger , Ovesen Christian , Willer Lasse , Nybing Janus Damm , Ægidius Karen , Marstrand Jacob , Meden Per , Rosenbaum Sverre , Folke Marie Norsker , Christensen Hanne , Christensen Anders 
Published: January 2018

ObjectivesTo find determining factors for persistent infarction signs in patients with transient ischaemic attack (TIA), herein initial diffusion lesion size, visibility on apparent diffusion coefficient (ADC) or fluid-attenuated inversion recovery (FLAIR) and location.DesignProspective cohort study of patients with clinical TIA receiving 3T-MRI within 72 hours of symptom onset and at 8-week follow-up.SettingClinical workflow in a single tertiary stroke centre between February 2012 and June 2014.Participants199 candidate patients were recruited, 64 patients were excluded due to non-TIA discharge diagnosis or no 8-week MRI. 122 patients completed the study.Primary outcome measuresThe primary outcome was visible persistent infarction defined as 8-week FLAIR hyperintensity or atrophy corresponding to the initial diffusion-weighted imaging (DWI) lesion.Results50 patients showed 84 initial DWI lesions. 29 (35%) DWI lesions did not result in infarction signs on 8-week FLAIR. 26 (90%, P<0.0001) reversing lesions were located in the cortical grey matter (cGM). cGM location (vs any other location) strongly predicted no 8-week infarction sign development (OR 0.02, 95% CI 0.001 to 0.17) or partial lesion area decrease (>30% of initial DWI-area, OR 14.10, 95% CI 3.61 to 54.72), adjusted for FLAIR-visibility, DWI-area, ADC-confirmation and time to scan (TTS) from symptom onset to baseline MRI. Acute FLAIR-visibility was a strong associated factor for persistent infarction signs (OR 33.06, 95% CI 2.94 to 1432.34). For cGM lesions area size was sole associated factor for persistent infarction signs with a 0.31 cm2(area under the curve (AUC), 0.97) threshold. In eight (16%) DWI-positive patients, all lesions reversed fully.Conclusions16% of DWI-positive patients and one-third of acute DWI lesions caused no persistent infarction signs, especially small cGM lesions were not followed by development of persistent infarction signs. Late MRI after TIA is likely to be less useful in the clinical setting, and it is dubious if the absence of old vascular lesions can be taken as evidence of no prior ischaemic attacks.Trial registration numberNCT01531946; Results.
Associations between physical behaviour patterns and levels of depressive symptoms, anxiety and well-being in middle-aged adults: a cross-sectional study using isotemporal substitution models
Authors: Dillon Christina B , McMahon Elaine , O’Regan Grace , Perry Ivan J 
Published: January 2018

ObjectiveTo examine the compositional effects of physical behaviour on mental health.DesignCross-sectional study.SettingA population-representative random sample (Mitchelstown cohort) was recruited from a large primary care centre in Mitchelstown, County Cork, Ireland.ParticipantsIn total 3807 potential participants were selected from the practice list. Following exclusion of duplicates, deaths and ineligibles, 3043 were invited to participate and of these, 2047 (49.2% men) completed the questionnaire and physical examination components of the baseline assessment during the study period (April 2010 and May 2011). Accelerometers were introduced into the study in January 2011. Of the 745 participants seen between January and May of 2011, 475 (44.6% men) subjects (response rate 64%) agreed to participate and of these 397 (46.1% men) had valid accelerometer data.Primary and secondary outcome measuresParticipants wore the wrist GENEActiv accelerometer for 7 consecutive days. Data were summarised into 60 s epochs and activity categorised as sedentary behaviour, light or moderate-to-vigorous physical activity (MVPA). Levels of depressive and anxiety symptoms were assessed using the Centre for Epidemiologic Studies Depression scale and the Hospital Anxiety and Depression Scale. Well-being was assessed using the WHO-5 well-being scale.ResultsIn adjusted isotemporal models, a 30 min increase in light activity per day was associated with a significant decrease in levels of anxiety symptoms (B=−0.34; 95% CI −0.64 to −0.04) and a significant increase in levels of well-being (B=0.58; 95% CI 0.05 to 1.11). No statistically significant associations were observed between any physical behaviour and depressive symptoms or when sedentary behaviour was substituted with MVPA (P>0.05).ConclusionAlthough based on a cross-sectional study, the findings suggest that substituting light activity for sedentary behaviour may have positive associations with symptoms of anxiety and reported well-being among middle-aged adults.
Impacts of Bicycle Infrastructure in Mid-Sized Cities (IBIMS): protocol for a natural experiment study in three Canadian cities
Authors: Winters Meghan , Branion-Calles Michael , Therrien Suzanne , Fuller Daniel , Gauvin Lise , Whitehurst David G T , Nelson Trisalyn 
Published: January 2018

IntroductionBicycling is promoted as a transportation and population health strategy globally. Yet bicycling has low uptake in North America (1%–2% of trips) compared with European bicycling cities (15%–40% of trips) and shows marked sex and age trends. Safety concerns due to collisions with motor vehicles are primary barriers.To attract the broader population to bicycling, many cities are making investments in bicycle infrastructure. These interventions hold promise for improving population health given the potential for increased physical activity and improved safety, but such outcomes have been largely unstudied. In 2016, the City of Victoria, Canada, committed to build a connected network of infrastructure that separates bicycles from motor vehicles, designed to attract people of ‘all ages and abilities’ to bicycling.This natural experiment study examines the impacts of the City of Victoria’s investment in a bicycle network on active travel and safety outcomes. The specific objectives are to (1) estimate changes in active travel, perceived safety and bicycle safety incidents; (2) analyse spatial inequities in access to bicycle infrastructure and safety incidents; and (3) assess health-related economic benefits.Methods and analysisThe study is in three Canadian cities (intervention: Victoria; comparison: Kelowna, Halifax). We will administer population-based surveys in 2016, 2018 and 2021 (1000 people/city). The primary outcome is the proportion of people reporting bicycling. Secondary outcomes are perceived safety and bicycle safety incidents. Spatial analyses will compare the distribution of bicycle infrastructure and bicycle safety incidents across neighbourhoods and across time. We will also calculate the economic benefits of bicycling using WHO’s Health Economic Assessment Tool.Ethics and disseminationThis study received approval from the Simon Fraser University Office of Research Ethics (study no. 2016s0401). Findings will be disseminated via a website, presentations to stakeholders, at academic conferences and through peer-reviewed journal articles.
Ketamine procedural sedation in the emergency department of an urban tertiary hospital in Dar es Salaam, Tanzania
Authors: Coralic Zlatan , Sawe Hendry R , Mfinanga Juma A , Cortez Alfredo , Koehl Jennifer , Siroker Hannah , Reynolds Teri A 
Published: January 2018

Study objectiveWe describe ketamine procedural sedations and associated adverse events in low-acuity and high-acuity patients in a resource-limited ED.MethodsThis was a prospective observational study of ketamine procedural sedations at the Emergency Medical Department at the Muhimbili National Hospital in Dar es Salaam, Tanzania. We observed consecutive procedural sedations and recorded patient demographics, medications, vital signs, pulse oximetry, capnography and a priori defined adverse events (using standard definitions in emergency medicine sedation guidelines). All treatment decisions were at the discretion of the treating providers who were blinded to study measurements to simulate usual care. Data collection was unblinded if predefined safety parameters were met. For all significant adverse and unblinding events, ketamine causality was determined via review protocol. Additionally, providers and patients were assessed for sedation satisfaction.ResultsWe observed 54 children (median 3 years, range 11 days–15 years) and 45 adults (median 33 years, range 18–79 years). The most common indications for ketamine were burn management in children (55.6%) and orthopaedic procedures in adults (68.9%). Minor adverse events included nausea/vomiting (12%), recovery excitation (11%) and one case of transient hypertension. There were nine (9%) patients who had decreased saturation readings (SpO2≤92%). There were three deaths, all in severely injured patients. After review protocol, none of the desaturations or patient deaths were thought to be caused by ketamine. No patient experienced ketamine-related laryngospasm, apnoea or permanent complications. Overall, ketamine was well tolerated and resulted in high patient and provider satisfaction.ConclusionIn this series of ketamine sedations in an urban, resource-limited ED, there were no serious adverse events attributable to ketamine.
Identification of rare diseases by screening a population selected on the basis of routine pathology results—the PATHFINDER project: lysosomal acid lipase/cholesteryl ester storage disease substudy
Authors: Reynolds Timothy M , Mewies Clare , Hamilton John , Wierzbicki Anthony S 
Published: January 2018

AimsLysosomal acid lipase deficiency (LALD) is an autosomal recessive disorder of cholesterol ester storage associated with hepatic disease, cirrhosis and accelerated atherosclerosis. Its prevalence in the general population, patients with dyslipidaemia and raised transaminases is unclear. This study attempted to identify the prevalence of LALD from patients with abnormal results in laboratory databases.MethodsElectronic laboratory databases were interrogated to identify from clinical biochemistry records patients with a phenotype of low high-density lipoprotein-cholesterol (≤0.85 mmol/L; 33 mg/dL) and with elevated alanine or aspartate transaminases (≥60 IU/L) on one occasion or more over a 3-year time interval. Patients were recalled, and a dried blood spot sample was collected for lysosomal acid lipase determination by a fluorimetric enzyme assay. Histopathology databases of liver biopsies were interrogated for patients with features of ‘microvesicular cirrhosis’ or ‘cryptogenic cirrhosis’ in the report. Histological blocks were sampled, and samples were analysed by next-generation sequencing for the presence of mutations in the LAL gene.ResultsSamples were obtained from 1825 patients with dyslipidaemia and elevated transaminases. No cases of LALD were identified. Liver biopsies were obtained from six patients. DNA extraction was successful from four patients. Two patients were homozygous for the LAL c.46A>C;p.Thr16Pro unclassified variant in exon 2.ConclusionsPathology databases hold routine information that can be used to identify patients with specific patterns of results or those who had biopsies to allow targeted testing for possible causes of disease. Biochemical screening suggests that the gene frequency of LAL deficiency in adults is less than 1 in 100.
Catalogue of inherited disorders found among the Irish Traveller population
Authors: Lynch Sally Ann , Crushell Ellen , Lambert Deborah M , Byrne Niall , Gorman Kathleen , King Mary D , Green Andrew , O’Sullivan Siobhan , Browne Fiona , Hughes Joanne , Knerr Ina , Monavari Ahmad A , Cotter Melanie , McConnell Vivienne P M , Kerr Bronwyn , Jones Simon A , Keenan Catriona , Murphy Nuala , Cody Declan , Ennis Sean , Turner Jackie , Irvine Alan D , Casey Jillian 
Published: January 2018

Background Irish Travellers are an endogamous, nomadic, ethnic minority population mostly resident on the island of Ireland with smaller populations in Europe and the USA. High levels of consanguinity result in many rare autosomal recessive disorders. Due to founder effects and endogamy, most recessive disorders are caused by specific homozygous mutations unique to this population. Key clinicians and scientists with experience in managing rare disorders seen in this population have developed a de facto advisory service on differential diagnoses to consider when faced with specific clinical scenarios.Objective(s) To catalogue all known inherited disorders found in the Irish Traveller population.Methods We performed detailed literature and database searches to identify relevant publications and the disease mutations of known genetic disorders found in Irish Travellers.Results We identified 104 genetic disorders: 90 inherited in an autosomal recessive manner; 13 autosomal dominant and one a recurring chromosomal duplication.Conclusion We have collated our experience of inherited disorders found in the Irish Traveller population to make it publically available through this publication to facilitate a targeted genetic approach to diagnostics in this ethnic group.
Nomenclatural acts for some Neotropical Tachinidae (Diptera)
Authors: Nihei Silvio Shigueo , Dios Rodrigo De Vilhena Perez 
Published: January 2018

New replacement names and synonymies are proposed for Neotropical Tachinidae, mainly from Brazil. The following 13 new replacement names are proposed for junior secondary homonyms: Jurinella neobesa, new name for Jurinella obesa (Townsend, 1928) (preocc. Wiedemann, 1830); Archytas wulpianus, new name for Archytas nigrocalyptratus (Wulp, 1888) (preocc. Macquart, 1846); Calodexia neofumosa, new name for Calodexia fumosa (Townsend, 1917) (preocc. Townsend, 1912); Calodexia bigoti, new name for Calodexia flavipes (Bigot, 1889) (preocc. Schiner, 1868); Eucelatoria paracarinata, new name for Eucelatoria carinata (Townsend, 1927) (preocc. Townsend, 1919); Eucelatoria currani, new name for Eucelatoria carinata (Curran, 1926) (preocc. Townsend, 1919); Lixophaga opsiangusta, new name for Lixophaga angusta (Townsend, 1927:294) (preocc. Townsend, 1927:284); Lixophaga thompsoniana, new name for Lixophaga fumipennis (Thompson, 1968) (preocc. Townsend, 1927); Lixophaga townsendiana, new name for Lixophaga fumipennis (Townsend, 1928) (preocc. Townsend, 1927); Myiopharus argentata, new name for Myiopharus argentescens (Townsend, 1935) (preocc. Townsend, 1927); Phyllophilopsis disgracilis, new name for Phyllophilopsis gracilis (Townsend, 1927) (preocc. Townsend, 1919); Phasia townsendiana, new name for Phasia brasiliana (Townsend, 1937) (preocc. Townsend, 1929); and Phasia aurodysderci, new name for Phasia dysderci (Townsend, 1940) (preocc. Townsend, 1938). And the two following synonymies are proposed (reinstated): Jurinella ambigua (Macquart, 1851) = Jurinella obesa (Wiedemann, 1830); and Archytas analis (Macquart, 1843) = Archytas analis (Fabricius, 1905).
Estimates of Surface Waves Using Subsurface EM-APEX Floats under Typhoon Fanapi 2010
Authors: Hsu Je-Yuan , Lien Ren-Chieh , D’Asaro Eric A. , Sanford Thomas B. 
Published: January 2018

AbstractSeven subsurface Electromagnetic Autonomous Profiling Explorer (EM-APEX) floats measured the voltage induced by the motional induction of seawater under Typhoon Fanapi in 2010. Measurements were processed to estimate high-frequency oceanic velocity variance associated with surface waves. Surface wave peak frequency fp and significant wave height Hs are estimated by a nonlinear least squares fitting to , assuming a broadband JONSWAP surface wave spectrum. The Hs is further corrected for the effects of float rotation, Earth’s geomagnetic field inclination, and surface wave propagation direction. The fp is 0.08–0.10 Hz, with the maximum fp of 0.10 Hz in the rear-left quadrant of Fanapi, which is ~0.02 Hz higher than in the rear-right quadrant. The Hs is 6–12 m, with the maximum in the rear sector of Fanapi. Comparing the estimated fp and Hs with those assuming a single dominant surface wave yields differences of more than 0.02 Hz and 4 m, respectively. The surface waves under Fanapi simulated in the WAVEWATCH III (ww3) model are used to assess and compare to float estimates. Differences in the surface wave spectra of JONSWAP and ww3 yield uncertainties of <5% outside Fanapi’s eyewall and >10% within the eyewall. The estimated fp is 10% less than the simulated before the passage of Fanapi’s eye and 20% less after eye passage. Most differences between Hs and simulated are <2 m except those in the rear-left quadrant of Fanapi, which are ~5 m. Surface wave estimates are important for guiding future model studies of tropical cyclone wave–ocean interactions.
The Effect of Nasoalveolar Molding on Nasal Airway Anatomy
Authors: Massie Jonathan P. , Bruckman Karl , Rifkin William J. , Runyan Christopher M. , Shetye Pradip R. , Grayson Barry , Flores Roberto L. 
Published: January 2018

Objective: To determine the effects of nasoalveolar molding (NAM) on nasal airway architecture. Design: Retrospective case-control study of patients with unilateral cleft lip treated with NAM vs without NAM. Setting: Tertiary referral center specializing in cleft and craniofacial care. Patients, Participants, and Interventions: Thirty-six patients with complete unilateral cleft lip and alveolus: 19 with NAM therapy and 17 without NAM therapy. Main Outcome Measures: Cone beam computed tomography (CBCT) scans were compared in multiple coronal sections and were evaluated for linear and angular septal deviation, inferior turbinate hypertrophy, and linear and 2-dimensional airway area. Results: There were no significant differences in linear or angular septal deviation, inferior turbinate area, linear stenosis, or airway area between NAM- and non-NAM-treated patients. Conclusions: NAM effectively molds the external nasal cartilage and structures but may have limited effects on internal nasal structures.