bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of Gaia radial-velocity standards: stability and new substellar companion candidates
Authors: Boulkaboul A , Damerdji Y , Morel T , Frémat Y , Soubiran C , Gosset E , Abdelatif T E
Published: September 2022

Our main aim is to test the non-variability of the radial velocity (RV) of a sample of 2351 standard stars used for wavelength calibration of the Radial Velocity Spectrometer (RVS) instrument onboard Gaia. In this paper, we present the spectroscopic analysis of these stars with the determination of their physical parameters by matching observed and synthetic spectra. We estimate the offset between different instruments after determining the shift between measured and archived RVs since the instrument pipelines use various numerical masks. Through the confirmation of the stability of the target RVs, we find 68 stars with a long-term variation having an acceleration that exceeds $10 \, \rm {m\, s^{-1}\,yr^{-1}}$. This suggests a barycentric reflex motion caused by a companion. As activity phenomena may be the source of periodic and trend-like RV variations in stars with putative planetary companions, we analysed various activity indicators in order to check their correlations to the RV changes. Among the trend stars, 18 have a trend model scatter greater than $100 \, \rm {m\, s^{-1}}$ over a time span from 10 to 12 yr. We also confirm that six stars with known substellar companions have a total model scatter, 3σ, exceeding the threshold set by Gaia, that is, $300 \, \rm {m\, s^{-1}}$. In addition, TYC8963-01543-1, an SB2 star, has data scatter $\sigma = 176.6\, \rm {m\, s^{-1}}$. Four more other stars are revealed to be variable after combining data from different instruments. Despite the presence of low-amplitude changes, a very large fraction of our sample (98.8 per cent) appears suitable as RV calibrators for Gaia RVS.
Functional Divergence in a Multi-gene Family Is a Key Evolutionary Innovation for Anaerobic Growth in Saccharomyces cerevisiae
Authors: Krause David J , Hittinger Chris Todd
Published: September 2022

The amplification and diversification of genes into large multi-gene families often mark key evolutionary innovations, but this process often creates genetic redundancy that hinders functional investigations. When the model budding yeast Saccharomyces cerevisiae transitions to anaerobic growth conditions, the cell massively induces the expression of seven serine/threonine-rich anaerobically-induced cell wall mannoproteins (anCWMPs): TIP1, TIR1, TIR2, TIR3, TIR4, DAN1, and DAN4. Here, we show that these genes likely derive evolutionarily from a single ancestral anCWMP locus, which was duplicated and translocated to new genomic contexts several times both prior to and following the budding yeast whole genome duplication (WGD) event. Based on synteny and their phylogeny, we separate the anCWMPs into four gene subfamilies. To resolve prior inconclusive genetic investigations of these genes, we constructed a set of combinatorial deletion mutants to determine their contributions toward anaerobic growth in S. cerevisiae. We found that two genes, TIR1 and TIR3, were together necessary and sufficient for the anCWMP contribution to anaerobic growth. Overexpressing either gene alone was insufficient for anaerobic growth, implying that they encode non-overlapping functional roles in the cell during anaerobic growth. We infer from the phylogeny of the anCWMP genes that these two important genes derive from an ancient duplication that predates the WGD event, whereas the TIR1 subfamily experienced gene family amplification after the WGD event. Taken together, the genetic and molecular evidence suggests that one key anCWMP gene duplication event, several auxiliary gene duplication events, and functional divergence underpin the evolution of anaerobic growth in budding yeasts.
Progesterone suppresses podocalyxin partly by up-regulating miR-145 and miR-199 in human endometrial epithelial cells to enhance receptivity in in vitro models
Authors: Shekibi Manizha , Heng Sophea , Wang Yao , Samarajeewa Nirukshi , Rombauts Luk , Nie Guiying
Published: September 2022

Establishment of endometrial surface receptivity is crucial for the initiation of embryo implantation yet the molecular mechanisms are not well understood, especially in humans. We have recently discovered that podocalyxin (PODXL) is a critical negative regulator of human endometrial surface receptivity. PODXL is highly expressed in all epithelial and endothelial cells in the non-receptive endometrium, but down-regulated specifically in the luminal epithelium at receptivity. We have further shown that PODXL inhibits embryo implantation, and that PODXL down-regulation is essential for endometrial surface receptivity. Our previous study also indicated that progesterone down-regulates PODXL; however, the exact molecular regulations are unknown. Here, we investigated whether progesterone suppresses PODXL via microRNAs (miRNAs). We first bioinformatically predicted 13 miRNAs that may potentially target human PODXL, then experimentally determined whether any of these 13 miRNAs are altered in primary human endometrial epithelial cells (HEECs) by progesterone, and whether the identified miRNAs can affect PODXL expression in Ishikawa cells without progesterone and alter receptivity to embryo implantation. Progesterone significantly up-regulated miR-145 and miR-199 while suppressing PODXL in HEECs. When these two miRNAs were transfected into Ishikawa cells, both significantly down-regulated PODXL mRNA and protein in the absence of progesterone. Moreover, both miR-145 and miR-199 significantly enhanced receptivity of the Ishikawa monolayer to embryo implantation in in vitro models. This study thus provides in vitro evidence that PODXL is down-regulated by progesterone partly via miR-145 and miR-199 during the development of human endometrial epithelial receptivity. These results also reveal the likely importance of hormonal regulation of miRNAs for embryo implantation.
QUADRatlas: the RNA G-quadruplex and RG4-binding proteins database
Authors: Bourdon Sébastien , Herviou Pauline , Dumas Leïla , Destefanis Eliana , Zen Andrea , Cammas Anne , Millevoi Stefania , Dassi Erik
Published: September 2022

RNA G-quadruplexes (RG4s) are non-canonical, disease-associated post-transcriptional regulators of gene expression whose functions are driven by RNA-binding proteins (RBPs). Being able to explore transcriptome-wide RG4 formation and interaction with RBPs is thus paramount to understanding how they are regulated and exploiting them as potential therapeutic targets. Towards this goal, we present QUADRatlas (https://rg4db.cibio.unitn.it), a database of experimentally-derived and computationally predicted RG4s in the human transcriptome, enriched with biological function and disease associations. As RBPs are key to their function, we mined known interactions of RG4s with such proteins, complemented with an extensive RBP binding sites dataset. Users can thus intersect RG4s with their potential regulators and effectors, enabling the formulation of novel hypotheses on RG4 regulation, function and pathogenicity. To support this capability, we provide analysis tools for predicting whether an RBP can bind RG4s, RG4 enrichment in a gene set, and de novo RG4 prediction. Genome-browser and table views allow exploring, filtering, and downloading the data quickly for individual genes and in batch. QUADRatlas is a significant step forward in our ability to understand the biology of RG4s, offering unmatched data content and enabling the integrated analysis of RG4s and their interactions with RBPs.
Accuratein silicoconfirmation of rare copy number variant calls from exome sequencing data using transfer learning
Authors: Tan Renjie , Shen Yufeng
Published: September 2022

Exome sequencing is widely used in genetic studies of human diseases and clinical genetic diagnosis. Accurate detection of copy number variants (CNVs) is important to fully utilize exome sequencing data. However, exome data are noisy. None of the existing methods alone can achieve both high precision and recall rate. A common practice is to perform heuristic filtration followed by manual inspection of read depth of putative CNVs. This approach does not scale in large studies. To address this issue, we developed a transfer learning method, CNV-espresso, for in silico confirming rare CNVs from exome sequencing data. CNV-espresso encodes candidate CNVs from exome data as images and uses pretrained convolutional neural network models to classify copy number states. We trained CNV-espresso using an offspring–parents trio exome sequencing dataset, with inherited CNVs as positives and CNVs with Mendelian errors as negatives. We evaluated the performance using additional samples that have both exome and whole-genome sequencing (WGS) data. Assuming the CNVs detected from WGS data as a proxy of ground truth, CNV-espresso significantly improves precision while keeping recall almost intact, especially for CNVs that span a small number of exons. CNV-espresso can effectively replace manual inspection of CNVs in large-scale exome sequencing studies.
Hippocampal subfield morphology in regular hemodialysis patients
Authors: Chen Hui Juan , Qiu Jie , Qi Yonghui , Fu Lili , Fu Qingqing , Wu Wenyuan , Dai Ganmian , Chen Feng
Published: September 2022

Background

Hippocampal alterations have been implicated in the pathophysiology of cognitive impairment in hemodialysis patients. The hippocampus consists of several distinct subfields, and the molecular mechanisms underlying cognition might be associated with specific hippocampal subfield volume changes. However, this has not yet been investigated in hemodialysis patients. This study aimed to explore volumetric abnormalities in hippocampal subfields in regular hemodialysis patients.

Methods

High-resolution T1-weighted structural images were collected in 61 subjects including 36 hemodialysis patients and 25 healthy controls. A state-of-the-art hippocampal segmentation approach was adopted to segment the hippocampal subfields. Group differences in hippocampal subfield volumes were assessed in Python with a statsmodels module using an ordinary least squares regression with age and sex as nuisance effects.

Results

Hemodialysis patients had significantly smaller volumes in the bilateral hippocampus (P < .05/2, Bonferroni corrected), cornu ammonis 1 (CA1), CA4, granule cell and molecular layer of the dentate gyrus, hippocampus–amygdala transition area and molecular layer of the hippocampus than healthy controls (P < .05/24, Bonferroni corrected). Hemodialysis patients also had lower volumes in the left hippocampal tail and right fimbria than healthy controls (P < .05/24, Bonferroni corrected). Hippocampal subfield volumes were associated with neuropsychological test scores, the duration of disease and hemoglobin levels.

Conclusions

We found smaller hippocampal subfield volumes in hemodialysis patients, which were associated with impaired cognition, supporting their role in memory disturbance in the hemodialysis population. However, multiple clinical factors may have confounded the results, and therefore, the interpretation of these results needs to be cautious.
Cadmium, active smoking and renal function deterioration in patients with type 2 diabetes
Authors: Oosterwijk Milou M , Hagedoorn Ilse J M , Maatman Ronald G H J , Bakker Stephan J L , Navis Gerjan , Laverman Gozewijn D
Published: September 2022

Background

Cadmium is an established nephrotoxin, present in cigarette smoke. We investigated the hazards of cadmium concentration and smoking status on renal function deterioration. We furthermore discerned whether the association of cadmium concentration with renal function deterioration is attributable to smoking status.

Methods

Prospective analyses were performed in data of 226 patients of the DIAbetes and LifEstyle Cohort Twente-1 (DIALECT). Cadmium concentrations were determined from EDTA whole-blood. Smoking status was determined via a self-administered questionnaire. Renal function deterioration was defined as need for renal replacement therapy or a persistent decline of ≥30% in estimated glomerular filtration rate from baseline for at least 3 months. Multivariable Cox regression models were performed to calculate hazard ratios (HRs) for the association between smoking status, cadmium concentration and renal function deterioration.

Results

Median (interquartile range) whole-blood cadmium was 2.9 (1.9–5.1) nmol/L. Active smokers had significantly higher cadmium [7.4 (3.3–11.7) nmol/L] compared with never smokers [2.6 (1.6–4.2) nmol/L] and former smokers [2.8 (1.8–4.8) nmol/L]. During median follow-up for 6 (4–8) years, renal function deterioration occurred in 60 persons (27%). Both cadmium and active smoking were associated with an increased hazard for renal function deterioration [HR 1.37, 95% confidence interval (95% CI) 1.06–1.78 and 3.77, 95% CI 1.72–8.29, respectively]. In a multivariable model with both smoking status and cadmium concentration included, active smokers have an increased risk for renal function deterioration (HR 3.00, 95% CI 1.22–7.40), while the association between cadmium and renal function deterioration lost statistical significance (HR 1.16, 95% CI 0.87–1.54).

Conclusions

Active smoking is associated with progressive kidney disease in type 2 diabetes. The association between cadmium concentration and renal function deterioration in large part determined by smoking status. Extensive assessment of smoking status may be useful in patients with type 2 diabetesat high risk of kidney damage.
Antiretroviral Drug Resistance in HIV Sequences From People Who Inject Drugs and Men Who Have Sex With Men Across 21 Cities in India
Authors: Clipman Steven J , Solomon Sunil S , Srikrishnan Aylur K , McFall Allison M , Gomathi Selvamurthi , Saravanan Shanmugam , Anand Santhanam , Vasudevan Canjeevaram K , Kumar Muniratnam S , Celentano David D , Mehta Shruti H , Lucas Gregory M
Published: September 2022

Background

Drug resistance testing is limited in public-sector human immunodeficiency virus (HIV) care in India, and there are few systematic samplings for prevalent drug resistance mutations (DRMs), particularly among men who have sex with men (MSM) and people who inject drugs (PWID).

Methods

We conducted genotypic resistance testing on 915 HIV sequences sampled from viremic self-reported antiretroviral therapy (ART) experienced and naive PWID and MSM recruited from 21 cities across India in 2016–2017. We analyzed factors associated with resistance using logistic regression and evaluated evidence for transmitted resistance using phylogenetic analyses.

Results

Of the 915 participants sequenced, median age was 31, 436 were MSM, and 191 were ART experienced. Overall, 62.8% of ART-experienced participants and 14.4% of ART-naive participants were found to have low-level resistance or higher to 1 or more classes of drugs. Prevalence of tenofovir disoproxil fumarate resistance was 25.7% in ART-experienced participants and 1.11% in ART-naive participants. The highest proportion of drug resistance was seen across nucleoside reverse transcriptase inhibitors and nonnucleoside reverse transcriptase inhibitors, and resistance was significantly more common among MSM participants than PWID. Phylogenetic analyses revealed that 54.6% of ART-naive participants with resistance who clustered had shared DRMs, suggesting transmitted resistance may have occurred.

Conclusions

Patients experiencing virologic failure on first-line therapy switched blindly to tenofovir/lamivudine/dolutegravir may effectively be receiving dolutegravir monotherapy due to resistance to tenofovir and lamivudine. While dolutegravir is expected to have full activity in the majority of patients in India, follow-up is needed to understand how resistance may affect long-term outcomes.
The End Is Nigh: Failed Prophecy, Apocalypticism, and The Rationalization of Violence in New Religious Eschatologies
Authors: Partridge Christopher
Published: September 2022

In popular discourse, apocalypticism has been the feature most often associated with new religious movements. In the theologies of many of the prominent new religions, end-time discourse is conspicuous. Several terms are used by scholars to discuss apocalyptic beliefs, notably apocalypticism, millennialism, and millenarianism, all of which overlap, clustering around the same general eschatological focus—the end of the present world. In the study of new religions, the term apocalypticism has tended to refer to catastrophism and, more often than not, to eschatological scenarios which, despairing of a political or religious transformation of the world, look to cataclysmic intervention of a divine, otherworldly, or superhuman kind. This article discusses millenarian adventism and failed prophecy, Jehovah's Witness eschatology, apocalypticism and violence involving Aum Shinrikyo in Japan, and eschatology and violence.
Hell
Authors: Kvanvig Jonathan L.
Published: September 2022

The language of heaven and hell as well as the doctrines associated with this language have their origin in the great monotheistic religions of the Abrahamic tradition—Judaism, Christianity, and Islam. The doctrines of heaven and hell are doctrines concerning the afterlife. The philosophical issues surrounding these doctrines have much wider significance, however, for every religion promises certain benefits to its adherents, and those benefits require by way of contrast some costs incurred by those who do not receive those benefits. The doctrine of hell has a central place in any serious eschatology, and it is no longer true that this doctrine is one of the ignored aspects of eschatology. This article focuses on the problems arising for the doctrines in the great monotheistic traditions and especially within Christianity, although the issues discussed will arise for any religious tradition. It examines the four separable theses associated with the punishment model: punishment thesis, no-escape thesis, anti-universalism thesis, and eternal existence thesis.
Apocalyptic Eschatology in the Ancient World
Authors: Collins John J.
Published: September 2022

The category of “apocalyptic literature” was invented by the German New Testament scholar Friedrich Lücke in 1832 in the context of an introduction to the Book of Revelation. Lücke identified a small number of Jewish apocalyptic writings (Daniel, 1 Enoch, 4 Ezra, and the Sibylline Oracles) and also discussed some Christian apocalypses such as the Ascension of Isaiah. With the resurgence of interest in biblical theology after World War I, interest in the non-canonical literature subsided. A new wave of interest in this material arose in the 1960s, stimulated in part by the publication of the Dead Sea Scrolls. As yet, there has been relatively little sociological study of ancient apocalypticism, arguably because the data are inadequate. Perhaps the most urgent desideratum, however, is that the progress made in this area be brought to bear on the study of eschatology in the Hebrew Bible and especially in early Christianity. This article discusses apocalyptic eschatology in the ancient world. It considers the origins of apocalypticism, Zoroastrianism and apocalypticism, apocalyptic writings as a development of biblical prophecy, and wisdom and apocalypticism.
The Eschatology of the New Testament Church
Authors: Rowland Christopher
Published: September 2022

The term “eschatology” is used to describe the critical nature of human decisions, the fate of the individual believer's soul after death, the termination of this world order and a setting up of another, events like the last judgment and the resurrection of the dead, and a convenient way of referring to future hopes about the coming of God's kingdom on earth, irrespective of whether in fact it involves an ending of the historical process. It is in this last sense that eschatology is being used in this article, as a shorthand way of referring to this future hope and its fulfillment, which was an important feature of many texts from the Second Temple period. This article examines the evidence which indicates the importance of eschatology in the New Testament writings. It also surveys the eschatological elements in the Gospels, the Pauline letters, and the Book of Revelation. The article concludes by assessing the degree to which the failure of early Christianity's eschatological hopes contributed to a change in the pattern of Christian faith and practice.
Eschatology and the Quest for the Historical Jesus
Authors: Viviano Benedict T.
Published: September 2022

This article discusses eschatology and the quest for the historical Jesus. It outlines the history of the debates over the exact character of the eschatological hope preached by Jesus and explains the terms “eschatology,” “apocalyptic,” and “kingdom.” The heavenly scene in Daniel 7:13–14 involves a transfer of power from one divine figure (the Ancient of Days) to another (the one like a Son of man). Also, early Jewish and Christian reflection on the kingdom of God and on God's plan of salvation for his people led them to a rough periodization, or theology of history. The modern quest for the historical Jesus, the first quest (1835–1906), began with the remarkable, extensive work by David Friedrich Strauss, The Life of Jesus (1835–1836). The second quest, from roughly 1919 to 1964, is the period of dialectical theology, form criticism, existentialist lives of Jesus, and the Luther renaissance. Beginning at the University of Chicago, the third quest for the historical Jesus began in the last two decades of the twentieth century.
Muslim Eschatology
Authors: Chittick William C.
Published: September 2022

The Koran speaks of death, the end of the world, and resurrection more than any other major scripture. The Hadith, or corpus of prophetic sayings, follows suit, as does the tradition in general. The relevant primary literature is vast, and nothing like an adequate survey of important texts has been written. As for the significance of Muslim eschatological teachings, most of the secondary literature seems to agree with Fritz Meier, who writes, “The basic concept of the ultimate origins and the hereafter in Islam... is not characterized by any particular originality, and as a system is no more satisfying than the corresponding Judeo-Christian one.” A good deal of more recent research, however, suggests that the original contributions of Muslim scholarship were just beginning to develop at the point where Meier leaves off, that is, around the time of Ibn Rushd (Averroes), who died in 1198. This article explores the eschatology of Muslims, realms of posthumous becoming, principles of Islamic theology, prophecy, eschatology, the two worlds, the Isthmus, the divine form, the soul, and the origin and return.
Buddhist Eschatology
Authors: Nattier Jan
Published: September 2022

If eschatology is understood to refer to “final things”—that is, the idea that the world will one day come to a definitive end—there is simply no parallel in the Buddhist tradition. This being said, Buddhist sources do refer to what Zwi Werblowsky has aptly termed “relative eschatologies.” On the cosmic level, one can speak of the end of a particular phase of manifestation or non-manifestation of the universe as a whole or, within this larger framework, the end of a specific cycle of devolution or evolution. On the historical level, Buddhist scriptures predict the demise of the Buddhist religion itself, holding that Buddhism—like all causally constructed phenomena—will eventually come to an end. This article deals with Buddhist eschatology, cosmic eschatology, cosmology and modernity, Mahāayāna developments, and the legacy of Śākyamuni Buddha and other Buddhas such as Maitreya.
Neurodevelopmental Outcomes in Preterm Infants with Intraventricular Hemorrhage in Canada
Authors: Shah V , Shah P , Kelly E , Mukerji A , Afifi J , El-Naggar W , Vincer M
Published: September 2022

BACKGROUND: Conflicting evidence exists in regards to outcomes of infants with mild IVH [subependymal hemorrhage (SEH) and IVH without ventricular dilatation (VD)] with recent reports suggesting poor outcomes.

OBJECTIVES: To compare 1) neurodevelopmental (ND) outcomes of infants < 29 wks GA with normal head ultrasound scan findings (Group 1: no IVH/PVL/VD to those with a) Group 2: SEH or IVH without VD, b) Group 3: IVH with VD (ventricle size > 10 mm) and c) Group 4: persistent intraparenchymal echogenicity (IPE) or lucency with or without IVH and 2) composite outcome of death or ND impairment (NDI)/severe NDI (SNDI) at 18-24 months in these groups.

DESIGN/METHODS: Retrospective cohort study of data from Canadian Neonatal Network (CNN)and Canadian Neonatal Follow-up Network (CNFUN) from April 2010 to September 2011. NDI was defined as any one of Bayley III score < 85 (cognition, language or motor), cerebral palsy (CP) or visual/hearing impairment. SNDI was defined as Bayley III score < 70 for any of the 3 components, CP with GMFCS > 3, severe visual impairment <20/200 or hearing impairment needing aids/cochlear implants. Data for the 4 groups were compared using Chi-squared test or ANOVA as appropriate. Multivariable regression was conducted to obtain adusted OR (95% CI).

RESULTS: See tables on page e51.

CONCLUSION: In this large national cohort, infants with SEH and/or IVH without VD had similar outcomes to infants with no IVH. The risk of death or adverse ND outcome was significantly higher ininfants with IVH with VD and those with IPE.
Is There an App for That? Assessing the Quality and Content of Apps for Asthma Management Available In Canada
Authors: Carwana M , Yang C
Published: September 2022

BACKGROUND: Asthma is the most common chronic respiratory disease in Canada, with highest prevalence in children 5-17 years of age. The use of effective apps for asthma management for children and adolescents may decrease the significant morbidity of this disease. A wide range of apps designed to assist in the home management of asthma are available online. However, there are no published data assessing the quality and content of asthma apps for children and families in Canada.

OBJECTIVES: To evaluate apps targeted at children or parents for the active management of asthma based on quality, accuracy of content and presence of advertising.

DESIGN/METHODS: The iOS and Google Play stores were searched using the key terms “asthma”, “reactive airways”, “puffer”, and “wheeze”. Apps that were available in English or French, were interactive, were targeted at children or their families, and addressed the medical management of asthma were included. Apps were examined using a detailed data collection tool to assess usability and content. Quality criteria was based on a published, validated tool. Content was evaluated based on the Canadian Thoracic Society asthma guidelines.

RESULTS: A total of 95 apps were screened, and 11 met the inclusion criteria. Average app quality score was 3.65 (range 2.63 – 4.38) out of 5. One app used 7 out of 7 CTS criteria in assessing asthma control, one used 6, six used 5, and three used 4. 10 out of 11 apps had the capacity to track symptoms, which was linked to level of asthma control based on CTS/CPS criteria. 8 out of 11 apps had the capacity to record medication doses in a journal format and provided daily medication reminders. 6 apps had the capacity to create and save a personalized asthma action plan. All apps used medications available in Canada. The most functional app based on these criteria was asthmamd, followed by AsthmaSense. One app was funded but a pharmaceutical company and had industry logo, but no significant brand bias. No other apps had specific industry advertising. None were specifically designed for use by children or adolescents.

CONCLUSION: 11 relatively high-quality apps are available for asthma management for Canadian families. Of these apps, the ones that best match quality, adherence to CTS guidelines, and lack of marketing/branding are asthmamd and AsthmaSense. There exists a gap to create apps that are specifically targeted at children and adolescents with high functionality for managing asthma.
Relationship Between Kawasaki Disease, Common Infections and Myocardial Profiling
Authors: Le CK , Dionne A , Autmizguine J , Dahdah N
Published: September 2022

BACKGROUND: The diagnosis of Kawasaki disease (KD) is challenging due to similarities with infections, which often defers clinicians from diagnosing KD and administering intravenous immunoglobulins (IVIG). However, concurrent infection was reported in 1/3 patients with complete KD. No study has evaluated the prevalence of infection in patients with incomplete clinical criteria.

OBJECTIVES: The aim of the study was to describe the prevalence and nature of concurrent infections in patients with KD.

DESIGN/METHODS: A retrospective study including consecutive patients suspected for KD between 2008 and 2014 in a tertiary pediatric university hospital.

RESULTS: From 134 patients (3.3±2.7 yo), infectious workup was performed for 129 (96%) patients, and positive in 32 (25%). A diagnosis of infection was maintained at discharge in 28/126 (22%) patients, of which 13 (46%) had a positive workup. Infections were diagnosed in a similar proportion of patients with complete and incomplete KD (25% vs 18%, p=0.29). During clinical course, 70 (54%) patients received antibiotics, with treatment failure in 42 (63%). Patients who received antibiotics were more likely to be resistant to IVIG (34% vs 10%, p=0.001), and need steroids (20% vs 3%, p=0.006). Patients with IVIG resistance had a higher rate of coronary artery aneurysm or dilatation (69% vs 45%, p=0.03). Patients with an infectious diagnosis at discharge were less likely to received IVIG (100% vs 89%, p=0.01). NT pro-BNP Z-score, indicating myocardial inflammation, was similar between patients with and without infection (2.3±2.2 vs 2.7±1.6, p=0.37). Coronary artery dilatations (Z-score>2.5) at diagnosis were present in 6/28 (21%) of patients with infection, and 30/98 (31%) of those without infection (p=0.34), which persisted at convalescence in 2/28 (7%) and 9/98 (9%), respectively (p=0.74). Finally, coronary aneurysms were present in 1/28 (4%) of patients with infections, and 17/98 (17%) of those without (p=0.07).

CONCLUSION: KD and infection are not mutually exclusive, including cases with incomplete KD criteria. Recognizing that both can coexist will hopefully ensure timely IVIG treatment for patients.
Dry-Powder Inhaler Delivery of Aerosolized Tobramycin with in Vitro Models of Tracheostomized Paediatric Patients
Authors: Wee W , Tavernini S , Martin A , Amirav I , Majaesic C , Finlay W
Published: September 2022

BACKGROUND: Tracheostomies are not uncommon in the pediatric population and are necessary in situations such as long-term cardiorespiratory compromise or fixed airway obstructions. Delivery of aerosolized medication allows for directed therapy to the lungs and is an important component of therapeutic management. However there is surprisingly little literature that quantifies delivery of aerosol medication through tracheostomies. During Pseudomonas aeruginosa respiratory infections, tobramycin is frequently administered using nebulizers, like the PARI LC Plus (LC Plus), which are known to have drawbacks, most notably the time burden. Dry-powder inhalers, like the TOBI Podhaler (Podhaler), can deliverhigher payloads of medication to the airway and in a shorter time. Currently no data exists that evaluates aerosol delivery of drypower inhalers through tracheostomies.

OBJECTIVES: The aim of the study is to investigate and quantify the amount of aerosolized tobramycin delivered to the lungs of in vitro trache-ostomized spontaneously breathing pediatric patient models when using the Podhaler in comparison to the current gold-standard, the LC Plus nebulizer.

DESIGN/METHODS: In vitro tracheostomized models of a 6- and 12-year old trachea were created. Aerosol was delivered to the tracheos-tomy models with the LC Plus and Podhaler, using their respective breathing patterns. Aerosolized medication was captured on a Respirgard II filter placed at the distal end of the trachea (lung filter), the amount was quantified using a colorimetric tobramycin assay and expressed as a percent charge of emitted dose. Drug trapped on the lung filter represented the amount of aerosol delivered to the respiratory tract. Three devices of each type were tested in triplicate to ensure repeatability.

RESULTS: A total of 36 runs (LC Plus: 18, Podhaler: 18) were completed and demonstrated the Podhaler’s consistent outperformance of the LC Plus. The results are expressed as mean ± standard deviation in percent charge (LC Plus vs. Podhaler); all runs (24.1±3.7 vs. 86.6±8.7), 6-year old model (23.2±2.6 vs. 82.1±9.9) and 12-year old (24.1±4.5 vs. 86.6±4.2). The results were statistically significant (P-values <<< 0.01), based on an unpaired t-tests due to unequal variance.

CONCLUSION: The study’s findings demonstrate that the Podhaler significantly outperformed the LC plus in delivering tobramycin to in vitro pediatric tracheostomized models. These results can be generalized to the tracheostomized adult population, and suggest that tobramycin delivery using the Podhaler is a feasible option and a future clinical study is warranted.
Transition of Children with Medical Complexity To Adult Care: A Survey of Current Canadian Practices
Authors: Chan V , Major-Cook N
Published: September 2022

BACKGROUND: Children with medical complexity (CMC), among the most medically fragile and resource-intensive patients, are an ever-growing population. Unique barriers exist for successful transition of CMC to adult care. Transition care specific to CMC has not been previously studied.

OBJECTIVES: To describe transition policy and procedures used by Canadian pediatricians who care for CMC, and whether this is consistent with core elements of transition according to nationalguidelines. To identify pediatricians'; perceived barriers to successful transition of CMC.

DESIGN/METHODS: We conducted a 29-item online survey using REDCap of Canadian general pediatricians who provide transition care to CMC. Use of core elements of transition as per Canadian Paediatric Society (CPS) and American Academy of Pediatrics (AAP) statements, and perceived barriers to transition were measured using 5-point Likert scales. Descriptive analysis was performed using SAS 9.3.

RESULTS: The response rate was 30% (77/). 19% of pediatricians reported feeling satisfied with their success in transitioning CMC to adult care. 51% and 40% have read the CPS and AAP policy statements on transition, respectively. 22% have a specified set of procedures on transition for CMC at their institution. 23% performed assessments for transition readiness. In transition planning for capable CMC, 69% assessed knowledge of own medical condition and 54% assessed preparedness to navigate adult services independently. For CMC with neurocognitive disabilities, 65% discussed capacity and 53% reviewed care directives. 2% felt the legal process regarding capacity was easy to navigate for families, and 52% provided no legal resources to families during transition. 59% did not have existing relationships with adult practitioners willing to take on care coordination of CMC. 86% communicated with receiving adult practitioners upon transfer of care. Pediatricians' major perceived barriers to successful transition are listed in Table 1.

CONCLUSION: Only 1 in 5 Canadian pediatricians working with CMC reported satisfaction with the transition care they provide. Core elements of transition from national guidelines are inconsistently implemented, highlighting the need to develop evidence-based transition policy considering the unique needs and barriers experienced by CMC.
Parental Use of Sun Protection for Their Children – Does Skin Colour Matter?
Authors: Nag S , Tan M , Weinstein M
Published: September 2022

BACKGROUND: Excessive sun exposure during childhood years is a known risk factor for skin cancer. Fifty percent of lifetime UV exposure is acquired by age 19, highlighting the potential for prevention strategies in childhood. Existing guidelines from established pediatric, dermatology and cancer prevention societies are general and not specific to any skin phototype.

OBJECTIVES: Our primary objective was to compare the frequency of adequate sun protection used by parents of children with different skin phototypes. Our secondary objective was to explore parental attitudes and beliefs on sun safety for their children.

DESIGN/METHODS: Parents of children between the ages of 6 months to 6 years were systematically recruited. Parents received self-administered questionnaires containing 40-items that examine the amount of sun protection parents used on their children, as well as their attitudes and beliefs about sun safety. Parents were also requested to self-assess their child’s Fitzpatrick Phototype (FP), and based on this response, they were divided into two groups: “lighter-skinned” (FP I-III) and “darker-skinned” (FP IV-VI). Guidelines from the Canadian Dermatology Association (CDA) on sun safety were used to quantify adequate sun protection.

RESULTS: A total of 183 parents completed the questionnaires, and 150 eligible parents (the first 25 of each FP) were included in the study. Overall, only 17% of parents used adequate sun protection for their children. Parents of lighter-skinned children were significantly more likely to use adequate sun protection (OR=17.0). As their child got older, parents were also significantly less likely to use adequate sun protection for them (OR=0.64). A significantly larger portion of parents of lighter-skin children believe that sun exposure was harmful (OR=14.2) and perceived more value in sun protection (OR=14.2), whereas parents of darker-skin children were significantly more likely to believe that darker skin tones provided more sun protection (OR=4.1).

CONCLUSION: Our study suggests that parental sun protection efforts were overall low, but especially in parents of darker-skinned children. The identified underlying attitudes and beliefs can aid in the design and delivery of sun protection interventions in the future, to ensure sun safety for all children, especially in a multiracial population.
ÉVALUATION DE LA SÉCURITÉ DE L’IMPLANTATION D’UN PROTOCOLE DE PRISE EN CHARGE DE LA FIÈVRE SANS FOYER D’INFECTION BACTÉRIENNE SÉVÈRE CHEZ LES ENFANTS DE 3 À 36 MOIS À L’URGENCE
Authors: Brodeur G , Guimont C , Turgeon R , Caron J , Blouin L
Published: September 2022

HISTORIQUE: En pédiatrie, la fièvre est l’une des raisons de consultation les plus fréquemment rencontrée. Au Centre mère-enfant du CHU de Québec, un protocole est en place pour orienter la prise en charge des enfants de 0 à 36 mois avec fièvre sans foyer. Avant février 2012, le proto-cole impliquait d’administrer un antibiotique chez tous les patients avec critères laboratoire d’infection bactérienne. Par contre, l’incidence des bactériémies occultes et des infections bactériennes sévères ayant significa-tivement diminué depuis la vaccination extensive contre le pneumocoque, un nouveau protocole a été mis en place afin de diminuer le traitement antibiotique des patients avec fièvre sans foyer.

OBJECTIFS: Objectif principal : Parmi les enfants ayant des critères d’antibiothérapie empirique selon l’ancien protocole, comparer le nom-bre de patients ayant eu une modification de traitement (début ou modification d’une antibiothérapie intraveineuse) avant et après l’implantation du nouveau protocole.Objectif secondaire : Chez les enfants ayant une infection bactérienne sévère diagnostiquée lors du suivi, déterminer si l’évolution est similaire chez ceux ayant reçu ou non une antibiothérapie empirique.

MATÉRIELS ET MÉTHODE: Il s’agit d’une étude rétrospective de non-infériorité. Tous les enfants de 3 à 36 mois qui se sont présentés à l’urgence et qui ont été référés en médecine de jour avec un diagnostic de fièvre sans foyer ont été recrutés. Les résultats de l’investigation initiale, le diagnostic final, le nombre de visites en médecine de jour, la durée d’hospitalisation, l’initiation d’une antibiothérapie et la présence de complications graves ont été répertoriés afin de comparer les 2 groupes.

RÉSULTATS: Sur les 282 patients étudiés, 1 enfant dans le groupe pré-implantation et 2 enfants dans le groupe post-implantation ont eu une modification de traitement en cours de suivi (1 infection urinaire avec germe résistant dans le groupe pré-implantation et 2 bactériémies dans le groupe post-implantation). Aucun patient étudié n’a eu une évolution défavorable (choc, sepsis sévère, défaillance multiviscérale, décès) et aucune différence statistiquement significative n’a été observée dans le nombre d’échec au traitement, le taux d’hospitalisation et le nombre de visites en médecine de jour entre les 2 groupes.

CONCLUSION: Avec cette étude, nous avons démontré qu’il est sécuri-taire de ne pas administrer d’emblée un antibiotique à large spectre chez les enfants de 3 à 36 mois avec bon état général se présentant à l’urgence avec fièvre sans foyer.
Adherence to Diabetic Ketoacidosis Management Protocol: A Paediatric Centre Experience
Authors: Bourdages M , Barbe J , Cloutier D , Bouchard I , Gagné J
Published: September 2022

BACKGROUND: Paediatric diabetic ketoacidosis (DKA) management should be regulated by specific protocols. Following the most recent medical literature, our tertiary pediatric hospital was provided with such a DKA protocol in 2009.

OBJECTIVES: Assess the proportion of cases of DKA that are marked by non-adherence to our DKA management protocol (DKAp). Describe the proportion of patients developing hyperchloraemic acidosis (HCl) during acute treatment of DKA.

DESIGN/METHODS: We conducted a retrospective study by chart review. Deviations to DKAp were classified as minor or major according to their potential impact on patient security. Non-adherence to protocol was defined as the occurrence of ≥ 1 major deviation or ≥ 2 minor deviations.

RESULTS: Seventy-nine patients were included with a mean age of 9,7 years (±4,9). Forty-two (53,2%) were females. Majority of cases were new-onset diabetes (60/79, 75,9%). Within the known diabetic patients (19), the DKA precipitating factor was poor treatment compliance in 10 (52,6%), and insulin pump dysfunction in 4 (21%). Mild DKA (pH 7,21 – 7,30) occurred in 24 (30,4%) patients, moderate DKA (pH 7,11- 7,20) in 30 (38,0%) and severe DKA (pH ≤ 7,10) in 25 (31,6%). Continuous insulin drip was used in 73/79 (92,4%) cases. We observed ≥ 1 major deviation to DKAp in 37/73 (50,7%) cases, mostly failure to monitor hourly neurological status (32/69, 46,4%, 4 missing values) and inappropriate administration of 0,9% NaCl IV bolus in well-hydrated patients (5/73, 7%). Minor deviations (≥2) occurred in 66/73 (90,4%) patients; mostly failure to monitor urine ketones levels every 4 hours (66/73, 90,4%) and blood gas and serum electrolytes every 2 hours (33/73, 45,2%). Overall, non-adherence to protocol occurred in 69 (94,5%) cases. The following complications were observed: 7/73 (9.6%) hypoglycaemia and 1/73 (1.4%) CT scan suspected cerebral edema. No death occurred. Fifty-five patients over 73 (75,3%) experienced HCl, The mean time apparition of HCl was 4:41 hours from the insulin perfusion beginning, using a normal anion gap definition ≤14. The HCl occurrence was associated with a longer insulin perfusion length (with HCl: 17.1±9.1 hours; without HCl: 9.2±5.6 hours, p<0.002).

CONCLUSION: Non-adherence to our DKAp was observed in majority of cases. The establishment of a protocol does not guarantee its adherence and surveillance of its application is needed. More studies have to be done to understand the clinical impact of HCl and to suggest an appropriate IV fluid management.
Clinical and Serologic Patterns in a Large Canadian Paediatric Cohort with Celiac Disease, At Presentation and Follow-Up
Authors: Gould M , Dowhaniuk J , Arredondo J , Cheng J , Azzopardi P , Hu T , Mileski H , Carpenter A , Pai N , Brill H
Published: September 2022

BACKGROUND: Celiac Disease (CD) is a chronic illness involving an autoimmune response to gluten, leading to small intestinal inflammation in genetically susceptible individuals. A weakness in the North American pediatric CD literature exists around serologic outcomes after initiation of a gluten free diet (GFD). Only one published North American pediatric study looks at normalization of TTG after initiation of a GFD and only assessed TTG normalization at 6 months post diagnosis. Data is also limited on other clinical patters such as levels of anemia and BMI over the course of treatment of CD.

OBJECTIVES: We sought to characterize serologic and clinical patterns in CD over an extended course using one of the largest databases of pediatric CD in North America.

DESIGN/METHODS: A retrospective review of all patients diagnosed with CD at our institution from 1996-2014 was completed. Patients required biopsy-proven CD according to the Marsh criteria. Data abstracted included age at diagnosis, gender, reason for referral, comorbidities, family history of CD and autoimmune conditions, BMI, hemoglobin, MVC, fer-ritin, IgA and anti-TTG levels. A Cochran-Armitage trend test was used to trend anti-TTG and hemoglobin normalization over time

RESULTS: 227 patients were identified who met study criteria. Visits with associated anti-TTG or hemoglobin analysis were categorized by time since diagnosis. At 6-12 months, 12-17 months, 18-23 months, 24-29 months, 30-35 months and 36-41 months from diagnosis 66.7% (n=144), 75% (n=40), 85.6% (n= 76), 86.9 (n= 23), 93.5 (n=62) and 95% (n= 20) of patients had normalized their anti-TTG levels respectively from a baseline of 100% abnormal TTG and 5.7% (n=140), 7.3% (n=41), 5.1% (n=77), 5.0% (n=20), 1.6% (n=60) and 5.0% (n=20) had anemia versus 18% at presentation.

CONCLUSION: The small p-value (p=<0.0001) for the Cochran-Armitage test for anti-TTG normalization indicates the increased probability of a normalized anti-TTG as time from diagnosis increases. Knowledge of the slope of this trend could assist clinicians with better understanding the effectiveness of treatment for their patients. In this cohort, anti-TTG levels normalized over a broad time span, with increasing numbers of patients normalizing their anti-TTG through to the end of the study period. Further research goals aim to determine predictors of early anti-TTG normalization. In this cohort, the proportion of patient with anemia quickly decreased from a baseline of 18%, to general pediatric population levels between 6-12 months after treatment initiation and remained stable in this range through to the end of the study period with a non-significant p value (p=0.06) for trend over time.