bluuebunny/crossref_metadata_2025_split huggingface dataset:
S4.5b A randomized, double blind phase II proof-of-concept superiority trial of fosravuconazole 200 mg or 300 mg weekly dose versus itraconazole 400 mg daily, all three arms in combination with surgery, in patients with eumycetoma in Sudan—pharmacokinetic results
Authors: Brüggemann Roger , Nyaoke Borna , Ahmed Eiman Siddig , Siddig Emanwell Edwar , Egondi Thaddaeus , Oyieko Peelen , Bakhiet Sahar Mubarak , Zijlstra Eduard E , Fahal Ahmed H 
Published: September 2022

Abstract

S4.5 Mycetoma Clinical Trial on fosravuconazole treatment in eumycetoma– Top Line Results, September 22, 2022, 10:30 AM - 12:00 PM

Objective
To evaluate the pharmacokinetics (PK) of fosravuconazole (measured as ravuconazole) and itraconazole in patients with mild to moderate eumycetoma caused by Madurella mycetomatis using a non-compartmental PK analysis.

Methods
Participants received either 200 mg or 300 mg ravuconazole once weekly or 400 mg itraconazole daily for a total duration of 12 months. Plasma concentrations of ravuconazole and itraconazole were measured on day 1 of week 1, and on weeks 2, 3, 4, and months 2, 3, 6, and 12 (at end of treatment) for analysis of population PK. The exact time of dosing on the days of sample collection, and the exact time of sample collection within the collection time window, were recorded. Plasma concentrations were quantified using Ultraperformance Liquid Chromatography with fluorescence detection (UPLC-UV). Ravuconazole and itraconazole plasma concentration-time data was performed using a standard two stage approach with non-compartmental analysis. Derived exposure parameters of ravuconazole and itraconazole, including, but not limited to, Cmax and AUC at steady state (AUCs), were calculated. The effect of covariates, such as baseline characteristics/demographics, on PK were explored. AUCs were determined when at least three subsequent samples within one dosing interval were available.

Results
A total of 766 samples of ravuconazole in 68 participants and 226 samples of itraconazole in 36 participants were analyzed. The average concentration of ravuconazole (range) was 3.1 mg/l (0.01-12.33 mg/l), and for itraconazole was 1.59 mg/l (0.01-5.53 mg/l).
Detailed Pharmacokinetic results will be communicated and discussed in the oral presentation.
S6.3c Adaptive dynamics in experimental populations of Aspergillus nidulans
Authors: Nandimath Krithi , Auxier Ben , van den Heuvel Joost , Bastiaans Eric , Klatter Mirre , Slakhorst Marijke , Schoustra Sijmen , Debets Alfons J. M. , Nanjundiah Vidyanand , Zwaan Bas J. , Aanen Duur K. , de Visser JAGM 
Published: September 2022

Abstract

S6.3 Fungal adaptation and evolution, September 22, 2022, 4:45 PM - 6:15 PM

A total of 12 replicate populations initiated with a laboratory strain of the ascomycete fungus Aspergillus nidulans evolved on synthetic minimal glucose agar medium for 1 year, using weekly transfers of 1% of the produced asexual spores to fresh medium. This Aspergillus short-term evolution experiment (ASEX) was designed to understand how filamentous fungi adapt to growth on limited carbon in a spatially structured environment. We observed no systematic improvement in the fitness components tested and neither in the competitive fitness relative to the ancestor. Instead, we observed the repeated evolution of at least two morphotypes, with a fluffy-like (FL) or an ancestor-like (AL) colony morphology, leading to non-transitive fitness interactions among isolates in two selected populations. The genomic analyses of clones from all 12 populations at an early (week 10) and the final time point (week 52), show a clear role of natural selection during ASEX. We also observed a shared genetic basis and different timing of adaptation of AL and FL types. In addition, in most populations, both morphotypes do not form monophyletic groups, but they frequently disappear and re-evolve from ancestral forms of both types. Reduction in asexual spore yield, the most evident parallel phenotypic change found in all our evolved populations, is not due to the direct selection of genes involved in asexual reproduction. Instead, we argue that reduced spore yield is a pleiotropic effect of adaptive changes in metabolism.
S7.4a Vaccine-inducing lung resident CD4 + memory T cells are protective against Cryptococcus gattii infections
Authors: Ueno Keigo , Shimizu Kiminori , Chang Yun , Kwon-Chung June , Miyazaki Yoshitsugu 
Published: September 2022

Abstract

S7.4 Pathogenesis and host defense, September 23, 2022, 10:30 AM - 12:00 PM
Cryptococccus gattii is a highly virulent fungal pathogen that can cause cryptococcosis in previously healthy individuals. It is not fully understood how innate and acquired immune responses cooperatively suppress C. gattii infection. Hitherto, we have reported the following findings, (1) Specific environment for exposure of dectin-1 and dectin-2 ligands in cryptococcal cells (PLOS ONE 2019, PMID 31398236), (2) CD11b-mediated immune recognition for C. gattii and capsule dependent immune evasion from CD11b recognition (Eur J Immunol 2021, PMID 33728652), (3) Dendritic cells (DCs)-based vaccine induced lung resident memory Th17 cells and ameliorates C. gattii infection (Mucosal Immunol 2018, PMID 30279512), and (4) Neutrophil and opsonization can mediate fungicidal activity for cryptococcal cells (Med Mycol 2019, PMID 30668754). Based on these findings, we have inferred that induction of lung resident memory T cells (lung TRM) and TRM-driven myeloid cells including granulocytes is necessary for controlling this infection. Currently, we are developing new intranasal (IN) vaccines using highly immunogenic whole cell antigens and characterizing protective lung TRM induced by the vaccines. Just as with component vaccines, whole cell vaccines are also featured for cryptococcal infection because these are highly cross-reactive and protective against each serotype (Biol Pharm Bull 2020, PMID 32009111).

We developed two IN vaccines using whole cell antigen and adjuvant. Both vaccines induced IL-5-producing lung TRM and significantly reduced fungal burden in lungs and improved survival rates of mice following C. gattii infection, while not protective against C. neoformans infection. Although immune suppressive agent FTY720 can eliminate most circulating T cells and sustain tissue-resident subset, IN vaccines induced Th2-related immune response including eosinophils and IFN-γ independent granuloma, and reduced the fungal burden in lungs after the infection in the presence of FTY720. Vaccine-mediated protection was completely lost in the Rag-1 knockout mice deficient in T- and B-cells, while the fungal burden was reduced in the Rag-1 knockout mice after receiving the immunized CD4 + T cells in the adoptive transfer experiments. These results suggest that Th2-related lung TRM induced by IN vaccines are also protective against C. gattii infection as well as Th17-related counterparts induced by DC vaccine.
Prompt cusp formation from the gravitational collapse of peaks in the initial cosmological density field
Authors: White Simon D M 
Published: September 2022

ABSTRACT
I present an analytic model for the early post-collapse evolution of a spherical density peak on the coherence scale of the initial fluctuations in a universe filled with collisionless and pressure-free ‘dust’. On a time-scale which is short compared to the peak’s collapse time t0, its inner regions settle into an equilibrium cusp with a power-law density profile, ρ ∝ r−12/7. Within this cusp, the circular orbit period P at each radius is related to the enclosed mass M by P = t0(M/Mc)2/3 where Mc is a suitably defined characteristic mass for the initial peak. The relaxation mechanism which produces this cusp gives insight into those which are active in high-resolution simulations of first halo formation in cold or warm dark matter universes, and, indeed, a simple argument suggests that the same power-law index γ = −12/7 should describe the prompt cusps formed during the collapse of generic peaks, independent of any symmetry assumption. Further work is needed to investigate the additional factors required to explain the slightly flatter exponent, γ ≈ −1.5, found in high-resolution numerical simulations of peak collapse.
Protestant Theology
Authors: Sauter Gerhard 
Published: September 2022

Abstract
The doctrine of the last things concerns both the ultimate destiny of the human race and the end of the world of which humans are a part. It points to the coherence of God's mysteries and to the right way of perceiving salvation, to God's redemption of humanity through its calling into the community of faithful people, and finally to God's last judgment and radical renewal of the world. This concept attempts to offer comprehensive answers to a number of questions: What are the last things? Why are they the end? And where will we finally be? As a compilation of the subjects of hope, eschatology takes on the question: What may we hope—in the face of death? Yet the discussion of this question is embedded in the perception of God's acting from the beginning of world and time, which culminates in Jesus Christ's incarnation, death, and resurrection. This article deals with the theology of Protestants, eschatology and the destination of history, radical eschatology, and the views of Friedrich Schleiermacher and Karl Barth.
Early Onset Neonatal Sepsis in Canada: 2011-2012
Authors: Sgro M , Kobylianskii *A , Sankaran K , Tran D , Yudin M , Campbell D 
Published: September 2022

Abstract
BACKGROUND: Canadian and US studies suggest that the organisms responsible for early-onset neonatal sepsis (EONS) are changing, with an increase in Escherichia coli (EC) as well as antibiotic-resistant organisms. Current Canadian guidelines for prevention and treatment of EONS are based on Group B streptococcus (GBS) as the likely organism. Population-level data may inform updates to these national strategies.
OBJECTIVES: To determine the incidence, types of organisms and corresponding resistance patterns involved in EONS in Canada. To identify how the organisms are affected by maternal antibiotic prophylaxis and other factors.
DESIGN/METHODS: Cases of EONS (defined as positive blood and/or cerebrospinal fluid (CSF) culture at &lt;7 days of age) between January 2011 and December 2012 were identified through the Canadian Paediatric Surveillance Program (CPSP). Neonates were excluded if they were asymptomatic with a positive culture likely to be a contaminant, or if the CSF culture was positive as a result of an intracranial procedure.
RESULTS: Over the 2-year period, 127 cases meeting our criteria were identified, and there were 754,849 total Canadian live births. The incidence for EONS was 0.17/1000 live births. 79.5% of cases presented within the first 24 hours of life, while 15% presented between 72 h-7 days. GBS accounted for 41.7% of cases, while EC accounted for 35.4%. Resistance was noted in 33.9% of cases overall. 55.6% of EC were resistant, with ampicillin resistance being the most common. The species of infecting organism was significantly associated with gestational age, very low birth weight, age at presentation, the mother having received GBS prophylaxis, and rupture of membranes lasting more than 18 h. GBS was most common in term and EC in preterm neonates. The overall EONS case fatality rate was 11%, with most of these being deaths from EC.
CONCLUSION: Our study suggests a lower rate of EONS than historically suggested, with differing dominant organisms based on gestational ages of the neonates. Later ages at presentation and high rates of resistance especially among EC cases further complicate the picture. We recommend a review of the Canadian prevention and treatment guidelines based on our findings.
Changes in Pulmonary Function After A Caffeine Loading Dose and Extubation Outcome in Preterm Infants with Respiratory Distress Syndrome
Authors: Yusuf K , Elsharkawy A , Alshaikh B , Petan L , Vine M 
Published: September 2022

Abstract
BACKGROUND: Prolonged endotracheal intubation in preterm infants leads to adverse outcomes including bronchopulmonary dysplasia, pneumonia and sepsis. Extubating preterm infants early can lead to apneas, respiratory distress and hypoxemia with reintubation, a destabilizing and traumatic event. Identifying readiness for extubation would avoid these harmful events. Current clinical criteria perform poorly in predicting extu-bation outcome in preterm infants. Caffeine is used to facilitate extubation and also affects pulmonary function.
OBJECTIVES: To determine pulmonary functions before and after a caffeine loading dose in preterm infants &lt; 31 weeks gestation with respiratory distress syndrome (RDS) undergoing their first trial of extubation and use them to predict extubation outcome.
DESIGN/METHODS: We determined dynamic compliance (Cdyn), tidal volume (TV), minute ventilation (MV), and dynamic airway resistance (Rdyn) before and after a loading dose of 10 mg/kg of caffeine base in preterm infants &lt;31 weeks gestation with RDS prior to extubation. These measurements were taken as an average of ten non-distorted breaths with &lt; 10% endotracheal air leak. Infants were ventilated with the EvitaXl Neo (Draeger, Germany). Pulmonary function readings were downloaded from the ventilator. Extubation failure was defined as the need for reintubation within 72 h after extubation. Exclusion criteria included grade 3-4 intra-ventricular hemorrhage, sedation, pneumothorax, medications affecting pulmonary function, chromosomal and congenital malformations. Mann Whitney test was used for continuous variables and the χ2 or Fisher’s exact test for dichotomous data. A p value &lt;0.05 was considered significant.
RESULTS: Blood gas values and ventilator parameters were similar between the groups before extubation.There was significant improvement in pulmonary function after a loading dose caffeine. Amongst pulmonary functions, ratio of Cdyn before and after caffeine performed best in predicting extubation outcome with an area under the curve of 0.85 (95% CI 0.79-0.94).
CONCLUSION: Caffeine improves pulmonary function in preterm infants. A ratio of dynamic compliance before and after caffeine best predicted extu-bation outcome. Our results need validation in a prospective study.
Can We Predict Post-Hemorrhagic Ventricular Dilatation in Preterm Infants with Severe Intraventricular Hemorrhage?
Authors: Afifi J , Vincer M , Shah V , Ye XY , Shah P S , Barrington K , Kelly E , Piedboeuf B , El-Naggar W 
Published: September 2022

Abstract
BACKGROUND: The incidence of post-hemorrhagic ventricular dilatation (PHVD) remains high in preterm infants. Little is known about the risk factors for PHVD in infants with severe intraventricular hemorrhage (IVH).
OBJECTIVES: To determine the predictors of PHVD among preterm infants with severe IVH.
DESIGN/METHODS: We conducted a retrospective review of all pre-term infants (22+0 - 32+6 weeks) who were admitted to NICUs participating in the Canadian Neonatal Network between 2010 and 2014. Infants with severe IVH (IVH with ventricular dilatation or parenchymal bleeding) who survived ≥ 72 hours were included. Perinatal and neonatal risk factors were compared between infants with and without PHVD (lateral ventricles &gt;10 mm).
RESULTS: Of 16600 eligible infants, 1964 (11.8%) developed severe IVH. Of 1815 infants with severe IVH who survived ≥72 hours, 616 (34%) developed PHVD. Factors associated with occurrence of PHVD include: lower gestational age, small for gestational age, low 5 minute Apgar score, SNAPII score&gt;20, surfactant therapy, high frequency oscillatory ventilation (HFOV), inotropes and occurrence of pneumothorax. [table 1]. There were no differences between both groups in relation to antenatal steroids, multiple pregnancy, mode of delivery, birth weight, gender or the proportion received prophylactic indomethacin. Multivariate analysis showed low five-minute Apgar score and HFOV to be independent predictors of PHVD while maternal magnesium sulfate and small for gestation (SGA) to be protective against PHVD.[table 2].
CONCLUSION: Our study identified factors involved in the prediction of PHVD in a national cohort of preterm infants. The mechanisms by which these factors may impact PHVD need further investigation.
Increasing Incidence of Optic Nerve Hypoplasia/ Septo-Optic Dysplasia Spectrum: Geographic Clustering in Northern Canada
Authors: Rodd C , Khaper T , Bunge M , Clark I , Rafay M , Mhanni A , Kirouac N , Sharma A , Wicklow B 
Published: September 2022

Abstract
BACKGROUND: Since optic nerves and pituitary gland are embryologi-cally related, optic nerve hypoplasia (ONH) and septo-optic dysplasia (SOD) represent a clinical spectrum associated with visual impairment, pituitary deficiencies, and severe CNS structural malformations(SODplus). ONH is a leading cause of pediatric blindness in North America; genetic mutations are rarely observed. We recently perceived an increase in the number of children with SOD in our clinic. Similarly, several studies have reported a rise in the incidence of ONH/SOD in other jurisdictions.
OBJECTIVES: Our primary objectives were to examine trends in annual incidence in Manitoba and geographical clustering in our catchment area ofManitoba, NW Ontario and Nunavut.
DESIGN/METHODS: This was a retrospective 1996-2015 chart review from all medical services (Neurology, Ophthalmology, Endocrinology, Genetics) caring for these children to extract information pertaining to anthropometric measures, radiologic findings, parental characteristics, endocrinopathies, and neurologic symptoms. Postal codes were used to assign map co-ordinates and census-based material and social deprivation indices. Numbers of children from Manitoba only were used to calculate annual incidence. From 2010-2014, a Quality Assurance (QA) sub-study identified all pediatric radiology reports containing the words 'optic nerve'; the additional cases of ONH/SOD children not identified by chart review were used to better define the true incidence in Manitoba.
RESULTS: Ninety-three children were identified in our catchment area by chart review; Poisson regression confirmed a striking 1.11-fold annual increase (95%CI=1.07-1.16) or ~800% over two decades. The annual incidence (averaged 2010-2014) reached 53.3 per 100,000 affecting 1 in 1875 live births (chartdata). Including children identified by QA sub-study, the incidence rose to 113.3 per 100,000 live births in Manitoba. These are much higher than previously reported. Most children (~60%) had SODplus. Common presenting or follow-upfeatures were hypoglyce-mia, nystagmus, seizures, and developmental delay (50%); 40% had hormone deficiencies; 80% (75/93) had reduced visual acuity, typically bilateral. Many childrenwere born prematurelywith young (mean 21y: IQR 19-26y), primiparous mothers. Unhealthy maternal lifestyles and severe material deprivation were noted. There wasdisproportionate clustering in Northern Manitoba (3 times the average provincial rate) and in Nunavut.
CONCLUSION: We noted a dramatic rise in the annual incidence of ONH/SOD in Manitoba, NW Ontario and Nunavut, which is much higher than previous reports. This disorderwas strongly associated with poverty in northern communities. The temporal picture was consistent with environmental, nutritional, or toxic etiologies. About half of the children were severely affected with increased morbidity and health care burdens.
A Retrospective Evaluation of A Paediatric Consult Clinic Serving Uninsured Children in Canada
Authors: Suleman S , Humphreys J , Singer A , Markin R , Razik F , Au H 
Published: September 2022

Abstract
BACKGROUND: Children new to Canada may not have health insurance which limits access to health care and increases their vulnerability to poorer health outcomes. As part of a resident advocacy initiative, a monthly pediatric consult clinic was created within a community health clinic to serve uninsured children living in a suburb of a major Canadian city. At the time of its inception in 2009, 35% of patients seen in the health clinic did not have provincial health insurance and an additional 35-40% did not receive Interim Federal Health (IFH) that they were otherwise entitled to (Denburg et al., 2010).
OBJECTIVES: To describe the demographics and health issues of uninsured immigrant children referred to a pediatric consult clinic.
DESIGN/METHODS: This study is a retrospective chart review characterizing the patients seen from 2009 – 2013. We collected demographic information, presenting symptoms, diagnoses and clinical outcomes. After REB approval, 180 patients were identified and 159 charts were found. Data was extracted from each chart and coded into a database. Of these files, 38 were removed because of duplicate entries or if they were not seen in the clinic. A total of 121 charts were included in the final analysis. An audit was performed by a blinded reviewer to identify any discrepancies in transcription prior to descriptive analysis.
RESULTS: Over half (52.1%) of patients seen in our clinic were landed immigrants or Canadians, while 19.8% had refugee status. 49.3% of patients were in a 3-month waiting period for provincial health insurance, while 12.6% had IFH, 11.6% had OHIP and 21.5% had no insurance at all. Only 34% spoke English as their primary language. The top three presenting complaints were developmental, dermatologic and respiratory. The most common final diagnoses were psychiatric and behavioural, dermato-logic and nutritional. The majority of patients required counselling (67%), with 14% prescribed a short medication course and 20% requiring ongoing medication.
CONCLUSION: Almost 70% of patients seen had no insurance at the time of their visit, with most in the mandatory 3-month wait for provincial health coverage. Our study suggests that children still need access to health care during this period. The most common diagnoses related to mental health and development suggesting a high prevalence in immigrants and supporting the need to screen for these issues when caring for children new to Canada.