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1. CDK9 inhibition inhibits multiple oncogenic transcriptional and epigenetic pathways in prostate cancer

Author

Rahman, Razia, Rahaman, Muhammed H., Hanson, Adrienne R., Choo, Nicholas, Xie, Jianling, Townley, Scott L., Shrestha, Raj, Hassankhani, Ramin, Islam, Saiful, Ramm, Susanne, Simpson, Kaylene J., Risbridger, Gail P., Best, Giles, Centenera, Margaret M., Balk, Steven P., Kichenadasse, Ganessan, Taylor, Renea A., Butler, Lisa M., Tilley, Wayne D., Conn, Simon J., Lawrence, Mitchell G., Wang, Shudong, and Selth, Luke A.

Published
2024
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2. Impact of SARS-CoV-2 Infection on the Association Between Laboratory Tests and Severe Outcomes Among Hospitalized Children.

Author

Xie, Jianling, Kuppermann, Nathan, Florin, Todd, Tancredi, Daniel, Funk, Anna, Kim, Kelly, Salvadori, Marina, Yock-Corrales, Adriana, Shah, Nipam, Breslin, Kristen, Chaudhari, Pradip, Bergmann, Kelly, Ahmad, Fahd, Nebhrajani, Jasmine, Mintegi, Santiago, Gangoiti, Iker, Plint, Amy, Avva, Usha, Gardiner, Michael, Malley, Richard, Finkelstein, Yaron, Dalziel, Stuart, Bhatt, Maala, Kannikeswaran, Nirupama, Caperell, Kerry, Campos, Carmen, Sabhaney, Vikram, Chong, Shu-Ling, Lunoe, Maren, Rogers, Alexander, Becker, Sarah, Borland, Meredith, Sartori, Laura, Pavlicich, Viviana, Rino, Pedro, Morrison, Andrea, Neuman, Mark, Poonai, Naveen, Simon, Norma-Jean, Kam, April, Kwok, Maria, Morris, Claudia, Palumbo, Laura, Ambroggio, Lilliam, Navanandan, Nidhya, Eckerle, Michelle, Klassen, Terry, Payne, Daniel, Cherry, Jonathan, Waseem, Muhammad, Dixon, Andrew, Ferre, Isabel, and Freedman, Stephen

Subjects
C-reactive protein, COVID-19, SARS-CoV-2, child, lymphopenia, procalcitonin
Abstract

BACKGROUND: To assist clinicians with identifying children at risk of severe outcomes, we assessed the association between laboratory findings and severe outcomes among severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected children and determined if SARS-CoV-2 test result status modified the associations. METHODS: We conducted a cross-sectional analysis of participants tested for SARS-CoV-2 infection in 41 pediatric emergency departments in 10 countries. Participants were hospitalized, had laboratory testing performed, and completed 14-day follow-up. The primary objective was to assess the associations between laboratory findings and severe outcomes. The secondary objective was to determine if the SARS-CoV-2 test result modified the associations. RESULTS: We included 1817 participants; 522 (28.7%) SARS-CoV-2 test-positive and 1295 (71.3%) test-negative. Seventy-five (14.4%) test-positive and 174 (13.4%) test-negative children experienced severe outcomes. In regression analysis, we found that among SARS-CoV-2-positive children, procalcitonin ≥0.5 ng/mL (adjusted odds ratio [aOR], 9.14; 95% CI, 2.90-28.80), ferritin >500 ng/mL (aOR, 7.95; 95% CI, 1.89-33.44), D-dimer ≥1500 ng/mL (aOR, 4.57; 95% CI, 1.12-18.68), serum glucose ≥120 mg/dL (aOR, 2.01; 95% CI, 1.06-3.81), lymphocyte count

Published
2023

3. Liver transaminase concentrations in children with acute SARS-CoV-2 infection

Author

Sumner, Madeleine W, Florin, Todd A, Kuppermann, Nathan, Xie, Jianling, Tancredi, Daniel J, Freedman, Stephen B, and PERN, Pediatric Emergency Research Canada PERC–COVID-19 Study Teams of the Pediatric Emergency Research Network

Subjects
Digestive Diseases, Infectious Diseases, Vaccine Related, Biodefense, Pediatric, Prevention, Liver Disease, Lung, Emerging Infectious Diseases, Infection, Good Health and Well Being, Humans, Child, COVID-19, SARS-CoV-2, Liver Diseases, Alanine Transaminase, Liver transaminase, Aminotransferase, Hepatotoxicity, of the Pediatric Emergency Research Network PERN, Pediatric Emergency Research Canada PERC – COVID-19 Study Teams, Medical Biochemistry and Metabolomics, Clinical Sciences, General Clinical Medicine
Abstract

ObjectiveTo evaluate the relationship between SARS-CoV-2 infection and liver injury by comparing transaminase concentrations among children tested for SARS-CoV-2 and other respiratory viruses in pediatric emergency departments.Design & methodsEligible children were

Published
2023

4. Author Correction: CDK9 inhibition constrains multiple oncogenic transcriptional and epigenetic pathways in prostate cancer

Author

Rahman, Razia, Rahaman, Muhammed H., Hanson, Adrienne R., Choo, Nicholas, Xie, Jianling, Townley, Scott L., Shrestha, Raj, Hassankhani, Ramin, Islam, Saiful, Ramm, Susanne, Simpson, Kaylene J., Risbridger, Gail P., Best, Giles, Centenera, Margaret M., Balk, Steven P., Kichenadasse, Ganessan, Taylor, Renea A., Butler, Lisa M., Tilley, Wayne D., Conn, Simon J., Lawrence, Mitchell G., Wang, Shudong, and Selth, Luke A.

Published
2024
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5. Corticosteroids and Other Treatments Administered to Children Tested for SARS-CoV-2 Infection in Emergency Departments.

Author

Freedman, Stephen B, Kuppermann, Nathan, Funk, Anna L, Kim, Kelly, Xie, Jianling, Tancredi, Daniel, Dalziel, Stuart R, Neuman, Mark I, Mintegi, Santiago, Plint, Amy C, Gómez-Vargas, Jessica, Finkelstein, Yaron, Ambroggio, Lilliam, Klassen, Terry P, Salvadori, Marina, Malley, Richard, Payne, Daniel C, Florin, Todd A, and Pediatric Emergency Research Network-COVID-19 Study Team

Subjects
Pediatric Emergency Research Network-COVID-19 Study Team, Humans, Adrenal Cortex Hormones, Nucleic Acids, Cross-Sectional Studies, Adolescent, Child, Emergency Service, Hospital, SARS-CoV-2, COVID-19 Drug Treatment, COVID-19, adrenal cortex hormones, child, hospitalized, emergency service, hospital, Emerging Infectious Diseases, Pediatric, Vaccine Related, Prevention, Clinical Trials and Supportive Activities, Biodefense, Clinical Research, Lung, Infectious Diseases, Respiratory, child, hospitalized, emergency service, hospital, Paediatrics and Reproductive Medicine, Pediatrics
Abstract

ObjectiveWe sought to determine if corticosteroid administration is associated with a SARS-CoV-2 nucleic acid test-positive result and to describe therapies administered to SARS-CoV-2 infected children.MethodsWe collected cross-sectional data from participants recruited in 41 pediatric emergency departments (ED) in 10 countries between March 2020 and June 2021. Participants were

Published
2022

9. Reciprocal signaling between mTORC1 and MNK2 controls cell growth and oncogenesis

Author

Xie, Jianling, Shen, Kaikai, Jones, Ashley T., Yang, Jian, Tee, Andrew R., Shen, Ming Hong, Yu, Mengyuan, Irani, Swati, Wong, Derick, Merrett, James E., Lenchine, Roman V., De Poi, Stuart, Jensen, Kirk B., Trim, Paul J., Snel, Marten F., Kamei, Makoto, Martin, Sally Kim, Fitter, Stephen, Tian, Shuye, Wang, Xuemin, Butler, Lisa M., Zannettino, Andrew C. W., and Proud, Christopher G.

Published
2021
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10. The regulation of mammalian target of rapamycin

Author

Xie, Jianling and Herbert, Terence

Subjects
573.3774
Abstract

mTOR is a highly conserved Serine/Threonine protein kinase which couples to a variety of stimulatory signals to control both anabolic and catabolic cellular processes. It exists in two biochemically and functionally distinct multi-component complexes termed as mTORC1 and mTORC2. Increasing evidence indicates that both mTOR complexes play crucial roles in the regulation of pancreatic β-cell function and mass. For example, hormones like GLP-1 that augment intracellular cAMP ([cAMP]i) are able to activate mTORC1 in β-cells, and it has been shown that GLP-1 treatment can lead to an enhancement of β-cell proliferation. However, in other cell types such as hepatocytes, neurons and many cancer cell lines, increases in [cAMP]i lead to the inhibition of mTORC1 which coincides with an impairment of cell replication. Therefore, the aims of this thesis were to reveal how cAMP regulates mTOR and to elucidate the molecular mechanism upon which mTOR complexes control pancreatic β-cell mass. My data provides evidence that the PKB-mTORC1 pathway by GLP-1 positively regulates β-cell proliferation, and that prolonged rapamycin treatment results in an induction of β-cell death which is caused by the inhibition of mTORC2 rather than mTORC1. These results further elucidated the mechanism by which mTOR complexes control pancreatic β-cell mass and therefore contribute to the design of future treatment against diabetes mellitus. In addition, I have also shown that cAMP, in contrast to its effects in β-cells, inhibits both mTORC1 and 2 in mouse embryonic fibroblasts (MEFs) and human embryonic kidney (HEK293) cells by promoting complex dissociation and blocking mTOR kinase activity. Increases in [cAMP]i also inhibit protein synthesis and prevent cell cycle progression in MEFs. In conclusion, this work has further unravelled how mTOR complexes control pancreatic β-cell mass, and provided a rationale of using cAMP-inducing agents to treat cancer.

Published
2012

14. Predictors of Adherence to Short-Course Probiotics Among Children with Gastroenteritis who are Enrolled in a Clinical Trial

Author

Hurley, Katrina F., Fitzpatrick, Eleanor A., Xie, Jianling, Urquhart, Sarah, Farion, Ken J., Gouin, Serge, Schuh, Suzanne, Poonai, Naveen, Freedman, Stephen, Hurley, Katrina F., Fitzpatrick, Eleanor A., Xie, Jianling, Urquhart, Sarah, Farion, Ken J., Gouin, Serge, Schuh, Suzanne, Poonai, Naveen, and Freedman, Stephen

Abstract

Background: To improve our understanding of adherence to discharge medications in the ED and within research trials, we sought to quantify medication adherence and identify predictors thereof in children with acute gastroenteritis (AGE). Methods: We conducted a secondary analysis of a randomized trial of twice daily probiotic for 5 days. The population included previously healthy children aged 3–47 months with AGE. The primary outcome was patient-reported adherence to the treatment regimen, defined a priori as having received >70% of the prescribed doses. Secondary outcomes included predictors of treatment adherence and concordance between patient-reported adherence and the returned medication sachet counts.Results: After excluding participants with missing data on adherence, 760 participants were included in this analysis: 383 in the probiotic arm (50.4%); and 377 in the placebo arm (49.6%). Self-reported adherence was similar in both groups (77.0% in probiotic versus 80.3% in placebo). There was good agreement between self-reported adherence and sachet counts (87% within limits of agreement (-2.9 to 3.5 sachets) on the Bland-Altman plots). In the multivariable regression model, covariates associated with adherence were greater number of days of diarrhea post-emergency department visit, and the study site; covariates negatively associated with adherence were age 12-23 months, severe dehydration and greater total number of vomiting and diarrhea episodes after enrolment. Conclusions: Longer duration of diarrhea and study site were associated with higher probiotic adherence. Age 12-23 months, severe dehydration and greater number of vomiting and diarrhea episodes post enrolment negatively predicted treatment adherence.

Published
2023

17. Comparative Evaluation of Luminex xTAG® Gastrointestinal Pathogen Panel and Direct-From-Stool Real-Time PCR for Detection of C. difficile Toxin tcdB in Stool Samples from a Pediatric Population

Author

Tyrrell, Hannah, primary, Morin, Sarah B. N., additional, Lloyd, Colin D., additional, Parsons, Brendon, additional, Stokowski, Taryn, additional, Xie, Jianling, additional, Zhuo, Ran, additional, Lee, Bonita E., additional, Pang, Xiao-Li, additional, Freedman, Stephen B., additional, and Chui, Linda, additional

Published
2022
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18. Significantly Longer Shedding of Norovirus Compared to Rotavirus and Adenovirus in Children with Acute Gastroenteritis.

Author

Qiu, Yuanyuan, Freedman, Stephen B., Williamson-Urquhart, Sarah, Farion, Ken J., Gouin, Serge, Poonai, Naveen, Schuh, Suzanne, Finkelstein, Yaron, Xie, Jianling, Lee, Bonita E., Chui, Linda, and Pang, Xiaoli

Subjects
ROTAVIRUSES, NOROVIRUSES, ADENOVIRUSES, GASTROENTERITIS, VIRAL load, CANADA Day
Abstract

Worldwide, acute gastroenteritis (AGE) is a major cause of morbidity and mortality in children under 5 years of age. Viruses, including norovirus, rotavirus, and enteric adenovirus, are the leading causes of pediatric AGE. In this prospective cohort study, we investigated the viral load and duration of shedding of norovirus, rotavirus, and adenovirus in stool samples collected from 173 children (median age: 15 months) with AGE who presented to emergency departments (EDs) across Canada on Day 0 (day of enrollment), and 5 and 28 days after enrollment. Quantitative RT-qPCR was performed to assess the viral load. On Day 0, norovirus viral load was significantly lower compared to that of rotavirus and adenovirus (p < 0.001). However, on Days 5 and 28, the viral load of norovirus was higher than that of adenovirus and rotavirus (p < 0.05). On Day 28, norovirus was detected in 70% (35/50) of children who submitted stool specimens, while rotavirus and adenovirus were detected in 52.4% (11/24) and 13.6% (3/22) of children (p < 0.001), respectively. Overall, in stool samples of children with AGE who presented to EDs, rotavirus and adenovirus had higher viral loads at presentation compared to norovirus; however, norovirus was shed in stool for the longest duration. [ABSTRACT FROM AUTHOR]

Published
2023
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19. Intestinal Microbial Composition of Children in a Randomized Controlled Trial of Probiotics to Treat Acute Gastroenteritis

Author

Horne, Rachael G., primary, Freedman, Stephen B., additional, Johnson-Henry, Kathene C., additional, Pang, Xiao-Li, additional, Lee, Bonita E., additional, Farion, Ken J., additional, Gouin, Serge, additional, Schuh, Suzanne, additional, Poonai, Naveen, additional, Hurley, Katrina F., additional, Finkelstein, Yaron, additional, Xie, Jianling, additional, Williamson-Urquhart, Sarah, additional, Chui, Linda, additional, Rossi, Laura, additional, Surette, Michael G., additional, and Sherman, Philip M., additional

Published
2022
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20. Post–COVID-19 Conditions Among Children 90 Days After SARS-CoV-2 Infection

Author

Pediatría, Pediatria, Funk, Anna L., Kuppermann, Nathan, Florin, Todd A., Tancredi, Daniel J., Xie, Jianling, Kim, Kelly, Finkelstein, Yaron, Neuman, Mark I., Salvadori, Marina I., Yock-Corrales, Adriana, Breslin, Kristen A., Ambroggio, Lilliam, Chaudhari, Pradip P., Bergmann, Kelly R., Gardiner, Michael A., Nebhrajani, Jasmine R., Campos, Carmen, Ahmad, Fahd A., Sartori, Laura F., Navanandan, Nidhya, Kannikeswaran, Nirupama, Caperell, Kerry, Morris, Claudia R., Mintegi Raso, Santiago, Gangoiti, Iker, Sabhaney, Vikram J., Plint, Amy C., Klassen, Terry P., Avva, Usha R., Shah, Nipam P., Dixon, Andrew C., Lunoe, Maren M., Becker, Sarah M., Rogers, Alexander J., Pavlicich, Viviana, Dalziel, Stuart R., Payne, Daniel C., Malley, Richard, Borland, Meredith L., Morrison, Andrea K., Bhatt, Maala, Rino, Pedro B., Beneyto Ferre, Isabel, Eckerle, Michelle, Kam, April J., Chong, Shu-Ling, Palumbo, Laura, Kwok, Maria Y., Cherry, Jonathan C., Poonai, Naveen, Waseem, MD; Norma-Jean Simon, MPH, Waseem, Muhammad, Simon, Norma-Jean, Freedman, Stephen B., Pediatric Emergency Research Network–COVID-19 Study Team, Pediatría, Pediatria, Funk, Anna L., Kuppermann, Nathan, Florin, Todd A., Tancredi, Daniel J., Xie, Jianling, Kim, Kelly, Finkelstein, Yaron, Neuman, Mark I., Salvadori, Marina I., Yock-Corrales, Adriana, Breslin, Kristen A., Ambroggio, Lilliam, Chaudhari, Pradip P., Bergmann, Kelly R., Gardiner, Michael A., Nebhrajani, Jasmine R., Campos, Carmen, Ahmad, Fahd A., Sartori, Laura F., Navanandan, Nidhya, Kannikeswaran, Nirupama, Caperell, Kerry, Morris, Claudia R., Mintegi Raso, Santiago, Gangoiti, Iker, Sabhaney, Vikram J., Plint, Amy C., Klassen, Terry P., Avva, Usha R., Shah, Nipam P., Dixon, Andrew C., Lunoe, Maren M., Becker, Sarah M., Rogers, Alexander J., Pavlicich, Viviana, Dalziel, Stuart R., Payne, Daniel C., Malley, Richard, Borland, Meredith L., Morrison, Andrea K., Bhatt, Maala, Rino, Pedro B., Beneyto Ferre, Isabel, Eckerle, Michelle, Kam, April J., Chong, Shu-Ling, Palumbo, Laura, Kwok, Maria Y., Cherry, Jonathan C., Poonai, Naveen, Waseem, MD; Norma-Jean Simon, MPH, Waseem, Muhammad, Simon, Norma-Jean, Freedman, Stephen B., and Pediatric Emergency Research Network–COVID-19 Study Team

Abstract

IMPORTANCE Little is known about the risk factors for, and the risk of, developing post-COVID-19 conditions (PCCs) among children. OBJECTIVES To estimate the proportion of SARS-CoV-2-positive children with PCCs 90 days after a positive test result, to compare this proportion with SARS-CoV-2-negative children, and to assess factors associated with PCCs. DESIGN, SETTING, AND PARTICIPANTS This prospective cohort study, conducted in 36 emergency departments (EDs) in 8 countries between March 7, 2020, and January 20, 2021, included 1884 SARS-CoV-2-positive children who completed 90-day follow-up; 1686 of these children were frequency matched by hospitalization status, country, and recruitment date with 1701 SARS-CoV-2-negative controls. EXPOSURE SARS-CoV-2 detected via nucleic acid testing. MAIN OUTCOMES AND MEASURES Post-COVID-19 conditions, defined as any persistent, new, or recurrent health problems reported in the 90-day follow-up survey. RESULTS Of 8642 enrolled children, 2368 (27.4%) were SARS-CoV-2 positive, among whom 2365 (99.9%) had index ED visit disposition data available; among the 1884 children (79.7%) who completed follow-up, the median age was 3 years (IQR, 0-10 years) and 994 (52.8%) were boys. A total of 110 SARS-CoV-2-positive children (5.8%; 95% CI, 4.8%-7.0%) reported PCCs, including 44 of 447 children (9.8%; 95% CI, 7.4%-13.0%) hospitalized during the acute illness and 66 of 1437 children (4.6%; 95% CI, 3.6%-5.8%) not hospitalized during the acute illness (difference. 5.3%; 95% CI, 2.5%-8.5%). Among SARS-CoV-2-positive children, the most common symptom was fatigue or weakness (21 [1.1%]). Characteristics associated with reporting at least 1 PCC at 90 days included being hospitalized 48 hours or more compared with no hospitalization (adjusted odds ratio [aOR], 2.67 [95% CI, 1.63-4.38]); having 4 or more symptoms reported at the index ED visit compared with 1 to 3 symptoms (4-6 symptoms: aOR, 2.35 [95% CI, 1.28-4.31]; >= 7 symptoms: aOR, 4.59 [95% CI

Published
2022

21. Da-Chai-Hu-Tang Protects From Acute Intrahepatic Cholestasis by Inhibiting Hepatic Inflammation and Bile Accumulation via Activation of PPARα

Author

Xu, Shihao, primary, Qiao, Xi, additional, Peng, Peike, additional, Zhu, Ziyi, additional, Li, Yaoting, additional, Yu, Mengyuan, additional, Chen, Long, additional, Cai, Yin, additional, Xu, Jin, additional, Shi, Xinwei, additional, Proud, Christopher G., additional, Xie, Jianling, additional, and Shen, Kaikai, additional

Published
2022
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22. Post–COVID-19 Conditions Among Children 90 Days After SARS-CoV-2 Infection

Author

Funk, Anna L., Kuppermann, Nathan, Florin, Todd A., Tancredi, Daniel J., Xie, Jianling, Kim, Kelly, Finkelstein, Yaron, Neuman, Mark I., Salvadori, Marina I., Yock-Corrales, Adriana, Breslin, Kristen A., Ambroggio, Lilliam, Chaudhari, Pradip P., Bergmann, Kelly R., Gardiner, Michael A., Nebhrajani, Jasmine R., Campos, Carmen, Ahmad, Fahd A., Sartori, Laura F., Navanandan, Nidhya, Kannikeswaran, Nirupama, Caperell, Kerry, Morris, Claudia R., Mintegi Raso, Santiago, Gangoiti, Iker, Sabhaney, Vikram J., Plint, Amy C., Klassen, Terry P., Avva, Usha R., Shah, Nipam P., Dixon, Andrew C., Lunoe, Maren M., Becker, Sarah M., Rogers, Alexander J., Pavlicich, Viviana, Dalziel, Stuart R., Payne, Daniel C., Malley, Richard, Borland, Meredith L., Morrison, Andrea K., Bhatt, Maala, Rino, Pedro B., Beneyto Ferre, Isabel, Eckerle, Michelle, Kam, April J., Chong, Shu-Ling, Palumbo, Laura, Kwok, Maria Y., Cherry, Jonathan C., Poonai, Naveen, Waseem, MD, Norma-Jean Simon, MPH, Waseem, Muhammad, Simon, Norma-Jean, Freedman, Stephen B., and Pediatric Emergency Research Network–COVID-19 Study Team

Subjects
COVID-19, outcomes
Abstract

IMPORTANCE Little is known about the risk factors for, and the risk of, developing post-COVID-19 conditions (PCCs) among children. OBJECTIVES To estimate the proportion of SARS-CoV-2-positive children with PCCs 90 days after a positive test result, to compare this proportion with SARS-CoV-2-negative children, and to assess factors associated with PCCs. DESIGN, SETTING, AND PARTICIPANTS This prospective cohort study, conducted in 36 emergency departments (EDs) in 8 countries between March 7, 2020, and January 20, 2021, included 1884 SARS-CoV-2-positive children who completed 90-day follow-up; 1686 of these children were frequency matched by hospitalization status, country, and recruitment date with 1701 SARS-CoV-2-negative controls. EXPOSURE SARS-CoV-2 detected via nucleic acid testing. MAIN OUTCOMES AND MEASURES Post-COVID-19 conditions, defined as any persistent, new, or recurrent health problems reported in the 90-day follow-up survey. RESULTS Of 8642 enrolled children, 2368 (27.4%) were SARS-CoV-2 positive, among whom 2365 (99.9%) had index ED visit disposition data available; among the 1884 children (79.7%) who completed follow-up, the median age was 3 years (IQR, 0-10 years) and 994 (52.8%) were boys. A total of 110 SARS-CoV-2-positive children (5.8%; 95% CI, 4.8%-7.0%) reported PCCs, including 44 of 447 children (9.8%; 95% CI, 7.4%-13.0%) hospitalized during the acute illness and 66 of 1437 children (4.6%; 95% CI, 3.6%-5.8%) not hospitalized during the acute illness (difference. 5.3%; 95% CI, 2.5%-8.5%). Among SARS-CoV-2-positive children, the most common symptom was fatigue or weakness (21 [1.1%]). Characteristics associated with reporting at least 1 PCC at 90 days included being hospitalized 48 hours or more compared with no hospitalization (adjusted odds ratio [aOR], 2.67 [95% CI, 1.63-4.38]); having 4 or more symptoms reported at the index ED visit compared with 1 to 3 symptoms (4-6 symptoms: aOR, 2.35 [95% CI, 1.28-4.31]; >= 7 symptoms: aOR, 4.59 [95% CI, 2.50 8.44]); and being 14 years of age or older compared with younger than 1 year (aOR, 2.67 [95% CI, 1.43-4.99]). SARS-CoV-2-positive children were more likely to report PCCs at 90 days compared with those who tested negative, both among those who were not hospitalized (55 of 1295 [4.2%; 95% CI, 3.2%-5.5%] vs 35 of 1321[2.7%; 95% CI, 1.9%-3.7%]; difference, 1.6% [95% CI, 0.2%-3.0%]) and those who were hospitalized (40 of 391[10.2%; 95% CI, 7.4%-13.7%] vs 19 of 380 [5.0%; 95% CI, 3.0%-7.7%]; difference, 5.2% [95% CI, 1.5%-9.1%]). In addition, SARS-CoV-2 positivity was associated with reporting PCCs 90 days after the index ED visit (aOR, 1.63 [95% CI, 1.14-2.35]), specifically systemic health problems (eg, fatigue, weakness, fever; aOR, 2.44 [95% CI, 1.19-5.00]). CONCLUSIONS AND RELEVANCE In this cohort study, SARS-CoV-2 infection was associated with reporting PCCs at 90 days in children. Guidance and follow-up are particularly necessary for hospitalized children who have numerous acute symptoms and are older. This studywas supported by grants from the Canadian Institutes of Health Research (operating grant: COVID-19-clinical management); the Alberta Health Services-University of Calgary-Clinical Research Fund; the Alberta Children's Hospital Research Institute; the COVID-19 Research Accelerator Funding Track (CRAFT) Program at the University of California, Davis; and the Cincinnati Children's Hospital Medical Center Division of Emergency Medicine Small Grants Program. Dr Funk is supported by the University of Calgary Eyes-High PostDoctoral Research Fund. Dr Freedman is supported by the Alberta Children's Hospital Foundation Professorship in Child Health andWellness.

Published
2022

23. Outcomes of SARS-CoV-2–Positive Youths Tested in Emergency Departments

Author

Funk, Anna L., Florin, Todd A., Kuppermann, Nathan, Tancredi, Daniel J., Xie, Jianling, Kim, Kelly, Neuman, Mark I., Ambroggio, Lilliam, Plint, Amy C., Mintegi, Santiago, Klassen, Terry P., Salvadori, Marina I., Malley, Richard, Payne, Daniel C., Simon, Norma-Jean, Yock-Corrales, Adriana, Nebhrajani, Jasmine R., Chaudhari, Pradip P., Breslin, Kristen A., Finkelstein, Yaron, Campos, Carmen, Bergmann, Kelly R., Bhatt, Maala, Ahmad, Fahd A., Gardiner, Michael A., Avva, Usha R., Shah, Nipam P., Sartori, Laura F., Sabhaney, Vikram J., Caperell, Kerry, Navanandan, Nidhya, Borland, Meredith L., Morris, Claudia R., Gangoiti, Iker, Pavlicich, Viviana, Kannikeswaran, Nirupama, Lunoe, Maren M., Rino, Pedro B., Kam, April J., Cherry, Jonathan C., Rogers, Alexander J., Chong, Shu-Ling, Palumbo, Laura, Angelats, Carlos M., Morrison, Andrea K., Kwok, Maria Y., Becker, Sarah M., Dixon, Andrew C., Poonai, Naveen, Eckerle, Michelle, Wassem, Muhammad, Dalziel, Stuart R., and Freedman, Stephen B.

Subjects
Male, Adolescent, SARS-CoV-2, Research, Infant, Newborn, COVID-19, Infant, Pediatrics, Severity of Illness Index, Hospitalization, Online Only, COVID-19 Testing, Risk Factors, Child, Preschool, Odds Ratio, Humans, Female, Prospective Studies, Child, Emergency Service, Hospital, Original Investigation, Follow-Up Studies
Abstract

Key Points Question What proportion of SARS-CoV-2–positive youths tested in emergency departments (ED) experience severe outcomes (ie, intensive interventions, severe organ impairment, or death) within 14 days? Findings Among 3221 SARS-CoV-2–positive youths enrolled in a global prospective cohort study with outcome data, 3.3% had severe outcomes within 14 days. Across a subgroup of 2510 SARS-CoV-2–positive youths discharged home after testing, 0.5% had severe outcomes during the 2-week follow-up period. Meaning The findings of this study suggest that risk factors such as age, underlying chronic illness, and symptom duration may be useful for clinicians to consider when evaluating pediatric patients with SARS-CoV-2 infection., This cohort study investigates the prevalence of severe outcomes among youths aged 17 years or younger within 14 days of testing positive for SARS-CoV-2 in emergency departments in 8 countries., Importance Severe outcomes among youths with SARS-CoV-2 infections are poorly characterized. Objective To estimate the proportion of children with severe outcomes within 14 days of testing positive for SARS-CoV-2 in an emergency department (ED). Design, Setting, and Participants This prospective cohort study with 14-day follow-up enrolled participants between March 2020 and June 2021. Participants were youths aged younger than 18 years who were tested for SARS-CoV-2 infection at one of 41 EDs across 10 countries including Argentina, Australia, Canada, Costa Rica, Italy, New Zealand, Paraguay, Singapore, Spain, and the United States. Statistical analysis was performed from September to October 2021. Exposures Acute SARS-CoV-2 infection was determined by nucleic acid (eg, polymerase chain reaction) testing. Main Outcomes and Measures Severe outcomes, a composite measure defined as intensive interventions during hospitalization (eg, inotropic support, positive pressure ventilation), diagnoses indicating severe organ impairment, or death. Results Among 3222 enrolled youths who tested positive for SARS-CoV-2 infection, 3221 (>99.9%) had index visit outcome data available, 2007 (62.3%) were from the United States, 1694 (52.6%) were male, and 484 (15.0%) had a self-reported chronic illness; the median (IQR) age was 3 (0-10) years. After 14 days of follow-up, 735 children (22.8% [95% CI, 21.4%-24.3%]) were hospitalized, 107 (3.3% [95% CI, 2.7%-4.0%]) had severe outcomes, and 4 children (0.12% [95% CI, 0.03%-0.32%]) died. Characteristics associated with severe outcomes included being aged 5 to 18 years (age 5 to

Published
2022

26. 144 Characterizing the Pain Experience of Children with Acute Gastroenteritis Based on Identified Pathogens

Author

Ma, Keon, primary, Ali, Samina, additional, Xie, Jianling, additional, Maki, Claudia, additional, Lee, Bonita, additional, Chui, Linda, additional, Pang, Xiao-Li, additional, Zhuo, Ran, additional, Parsons, Brendon, additional, Vanderkooi, Otto G, additional, Poonai, Naveen, additional, MacDonald, Shannon E, additional, Tarr, Phillip, additional, and Freedman, Stephen, additional

Published
2021
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28. Comparative Evaluation of Luminex xTAG ® Gastrointestinal Pathogen Panel and Direct-From-Stool Real-Time PCR for Detection of C. difficile Toxin tcdB in Stool Samples from a Pediatric Population.

Author

Tyrrell, Hannah, Morin, Sarah B. N., Lloyd, Colin D., Parsons, Brendon, Stokowski, Taryn, Xie, Jianling, Zhuo, Ran, Lee, Bonita E., Pang, Xiao-Li, Freedman, Stephen B., and Chui, Linda

Subjects
CLOSTRIDIOIDES difficile, CHILD patients, POLYMERASE chain reaction, PERFORMANCE in children, TOXINS, INTESTINAL infections
Abstract

Detection of Clostridioides difficile toxins in patients with gastroenteritis has increasingly been accomplished through the use of enteric multiplex syndromic panels. Comparisons of the performance of these panels to both direct-from-stool (DFS) and culture-enriched stools followed by polymerase chain reaction (PCR) methods in pediatric populations are limited. Here, we compare the performance of the Luminex xTAG® Gastrointestinal Pathogen Panel (GPP) to our DFS in-house real-time PCR (DFS RT-PCR) assay for the detection of C. difficile toxin gene, tcdB, using 2641 stool specimens collected from children enrolled in the Alberta Provincial Pediatric EnTeric Infection Team (APPETITE) study in Alberta, Canada. We used culture enrichment followed by in-house RT-PCR to resolve discordant results between the two assays. We found excellent agreement (k = 0.89) between the GPP and our DFS RT-PCR assay: the positive percent agreement between the two assays was 97%, and the negative percent agreement was 99%. GPP, a multi-analyte platform can easily be implemented into a routine diagnostic laboratory for detecting enteric pathogens including C. difficile. [ABSTRACT FROM AUTHOR]

Published
2022
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29. A feedback loop between the androgen receptor and 6-phosphogluoconate dehydrogenase (6PGD) drives prostate cancer growth

Author

Gillis, Joanna L, primary, Hinneh, Josephine A, additional, Ryan, Natalie K, additional, Irani, Swati, additional, Moldovan, Max, additional, Quek, Lake-Ee, additional, Shrestha, Raj K, additional, Hanson, Adrienne R, additional, Xie, Jianling, additional, Hoy, Andrew J, additional, Holst, Jeff, additional, Centenera, Margaret M, additional, Mills, Ian G, additional, Lynn, David J, additional, Selth, Luke A, additional, and Butler, Lisa M, additional

Published
2021
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30. The composition of the gut microbiota following early-life antibiotic exposure affects host health and longevity in later life

Author

Lynn, Miriam A., primary, Eden, Georgina, additional, Ryan, Feargal J., additional, Bensalem, Julien, additional, Wang, Xuemin, additional, Blake, Stephen J., additional, Choo, Jocelyn M., additional, Chern, Yee Tee, additional, Sribnaia, Anastasia, additional, James, Jane, additional, Benson, Saoirse C., additional, Sandeman, Lauren, additional, Xie, Jianling, additional, Hassiotis, Sofia, additional, Sun, Emily W., additional, Martin, Alyce M., additional, Keller, Marianne D., additional, Keating, Damien J., additional, Sargeant, Timothy J., additional, Proud, Christopher G., additional, Wesselingh, Steve L., additional, Rogers, Geraint B., additional, and Lynn, David J., additional

Published
2021
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33. Probiotic stool secretory immunoglobulin A modulation in children with gastroenteritis: a randomized clinical trial

Author

Freedman, Stephen B, primary, Horne, Rachael, additional, Johnson-Henry, Kathene, additional, Xie, Jianling, additional, Williamson-Urquhart, Sarah, additional, Chui, Linda, additional, Pang, Xiao-Li, additional, Lee, Bonita, additional, Schuh, Suzanne, additional, Finkelstein, Yaron, additional, Gouin, Serge, additional, Farion, Ken J, additional, Poonai, Naveen, additional, Hurley, Katrina, additional, Schnadower, David, additional, and Sherman, Philip M, additional

Published
2021
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34. Differences in Illness Severity among Circulating Norovirus Genotypes in a Large Pediatric Cohort with Acute Gastroenteritis

Author

Bhavanam, Sudha, Freedman, Stephen, Lee, Bonita, Zhuo, Ran, Qiu, Yuanyuan, Chui, Linda, Xie, Jianling, Ali, Samina, Vanderkooi, Otto, Pang, Xiaoli, and (APPETITE), on behalf of the Alberta Provincial Pediatric Enteric Infection Team

Subjects
0301 basic medicine, Microbiology (medical), medicine.medical_specialty, viruses, 030106 microbiology, norovirus, medicine.disease_cause, Microbiology, Article, 03 medical and health sciences, symbols.namesake, fluids and secretions, children, genotypes, Virology, Internal medicine, Genotype, medicine, Illness severity, Clinical severity, lcsh:QH301-705.5, Sanger sequencing, business.industry, virus diseases, Acute gastroenteritis, 030104 developmental biology, lcsh:Biology (General), clinical severity, Cohort, Norovirus, symbols, Vomiting, medicine.symptom, business, gastroenteritis
Abstract

Norovirus is a major pathogen identified in children with acute gastroenteritis (AGE), little is known about the strain’s diversity and their clinical severity. Stool and/or rectal swabs were collected from children ≤18 years of age recruited at emergency departments (ED), and a provincial nursing advice phone line due to AGE symptoms in the province of Alberta, Canada between December 2014 and August 2018. Specimens were tested using a reverse transcription real time PCR and genotyped by Sanger sequencing. The Modified Vesikari Scale score (MVS) was used to evaluate the disease severity. The objectives are to identify the Genogroup and Genotype distribution and to compare illness severity between the GI and GII genogroups and to complete further analyses comparing the GII genotypes identified. GII.4 was the genotype most commonly identified. Children with GII.4 had higher MVS scores (12.0 (10.0, 14.0, p = 0.002)) and more prolonged diarrheal (5 days (3.0, 7.8)) and vomiting (3.2 days (1.7, 5.3, p &lt, 0.001)) durations compared to other non GII.4 strains. The predominant strain varied by year with GII.4 Sydney[P31] predominant in 2014/15, GII.4 Sydney[P16] in 2015/16 and 2017/18, and GII.3[P12] in 2016/17. Genogroup II norovirus strains predominated in children with AGE with variance between years, clinical severity associated with different strains varied with episodes being most severe among GII.4 infected children.

Published
2020
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35. A Clinical Epidemiology and Molecular Attribution Evaluation of Adenoviruses in Pediatric Acute Gastroenteritis: a Case-Control Study

Author

Pabbaraju, Kanti, primary, Tellier, Raymond, additional, Pang, Xiao-Li, additional, Xie, Jianling, additional, Lee, Bonita E., additional, Chui, Linda, additional, Zhuo, Ran, additional, Vanderkooi, Otto G., additional, Ali, Samina, additional, Tarr, Phillip I., additional, Funk, Anna, additional, and Freedman, Stephen B., additional

Published
2020
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36. Hematochezia in children with acute diarrhea seeking emergency department care – a prospective cohort study.

Author

Böhrer, Madeleine, Fitzpatrick, Eleanor, Hurley, Katrina, Xie, Jianling, Lee, Bonita E., Pang, Xiao‐Li, Zhuo, Ran, Parsons, Brendon D., Berenger, Byron M., Chui, Linda, Tarr, Phillip I., Ali, Samina, Vanderkooi, Otto G., Freedman, Stephen B., Zemek, Roger, Newton, Mandi, Meckler, Garth, Poonai, Naveen, Bhatt, Maala, and Maki, Kate

Subjects
DIARRHEA, CAREGIVERS, CONFIDENCE intervals, INTRAVENOUS therapy, GASTROINTESTINAL hemorrhage, MEDICAL care use, COMPARATIVE studies, VOMITING, EMERGENCY medical services, DESCRIPTIVE statistics, VIRUS diseases, BACTERIAL diseases, ACUTE diseases, LONGITUDINAL method, SECONDARY analysis, SYMPTOMS, CHILDREN
Abstract

Objectives: Although the passage of blood in stools in children represents a medical emergency, children seeking emergency department (ED) care remain poorly characterized. Our primary objective was to compare clinical characteristics and etiologic pathogens in children with acute diarrhea with and without caregiver‐reported hematochezia. Secondary objectives were to characterize interventions and resource utilization. Methods: We conducted a secondary analysis of the Alberta Provincial Pediatric EnTeric Infection TEam (APPETITE) database. Children <18 years presenting to two pediatric EDs within a 24‐hour period and <7 days of symptoms were consecutively recruited. Results: Of 1,061 participants, 115 (10.8%) reported hematochezia at the enrollment visit at which time those with hematochezia, compared to those without, had more diarrheal episodes/24‐hour period (9 vs. 6; difference: 2; 95% confidence interval [CI]: 2.0, 4.0; p < 0.001), and were less likely to have experienced vomiting (54.8% vs. 80.2%; difference: −25.4; 95% CI: −34.9, −16.0; p < 0.001). They were more likely to receive intravenous fluids (33.0% vs. 17.9%; difference: 15.2; 95% CI: 6.2, 24.1; p < 0.001) and require repeat health care visits (45.5% vs. 34.7%; difference: 10.7; 95% CI: 0.9, 20.6; p = 0.03). A bacterial pathogen was identified in 33.0% of children with hematochezia versus 7.9% without (difference: 25.1; 95% CI: 16.3, 33.9; p < 0.001); viruses were detected in 31.3% of children with hematochezia compared to 72.3% in those without (difference: −41.0%, 95% CI: −49.9, −32.1; p < 0.001). Conclusion: In children with acute diarrhea, caregiver report of hematochezia, compared to the absence of hematochezia, was associated with more diarrheal but fewer vomiting episodes, and greater resource consumption. The former group of children was also more likely to have bacteria detected in their stool. [ABSTRACT FROM AUTHOR]

Published
2022
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38. Reciprocal signaling between mTORC1 and MNK2 controls cell growth and oncogenesis

Author

Xie, Jianling, primary, Shen, Kaikai, additional, Jones, Ashley T., additional, Yang, Jian, additional, Tee, Andrew R., additional, Shen, Ming Hong, additional, Yu, Mengyuan, additional, Irani, Swati, additional, Wong, Derick, additional, Merrett, James E., additional, Lenchine, Roman V., additional, De Poi, Stuart, additional, Jensen, Kirk B., additional, Trim, Paul J., additional, Snel, Marten F., additional, Kamei, Makoto, additional, Martin, Sally Kim, additional, Fitter, Stephen, additional, Tian, Shuye, additional, Wang, Xuemin, additional, Butler, Lisa M., additional, Zannettino, Andrew C. W., additional, and Proud, Christopher G., additional

Published
2020
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39. The Lifeact-EGFP mouse is a translationally controlled fluorescent reporter of T cell activation

Author

Galeano Niño, Jorge Luis, primary, Tay, Szun S., additional, Tearle, Jacqueline L. E., additional, Xie, Jianling, additional, Govendir, Matt A., additional, Kempe, Daryan, additional, Mazalo, Jessica, additional, Drew, Alexander P., additional, Colakoglu, Feyza, additional, Kummerfeld, Sarah K., additional, Proud, Christopher G., additional, and Biro, Maté, additional

Published
2020
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40. Regulation of the Elongation Phase of Protein Synthesis Enhances Translation Accuracy and Modulates Lifespan.

Author

Xie, Jianling, de Souza Alves, Viviane, von der Haar, Tobias, O'Keefe, Louise, Lenchine, Roman V, Jensen, Kirk B, Liu, Riu, Coldwell, Mark J, Wang, Xuemin, Proud, Christopher G., Xie, Jianling, de Souza Alves, Viviane, von der Haar, Tobias, O'Keefe, Louise, Lenchine, Roman V, Jensen, Kirk B, Liu, Riu, Coldwell, Mark J, Wang, Xuemin, and Proud, Christopher G.

Abstract

Maintaining accuracy during protein synthesis is crucial to avoid producing misfolded and/or non-functional proteins. The target of rapamycin complex 1 (TORC1) pathway and the activity of the protein synthesis machinery are known to negatively regulate lifespan in many organisms, although the precise mechanisms involved remain unclear. Mammalian TORC1 signaling accelerates the elongation stage of protein synthesis by inactivating eukaryotic elongation factor 2 kinase (eEF2K), which, when active, phosphorylates and inhibits eEF2, which mediates the movement of ribosomes along mRNAs, thereby slowing down the rate of elongation. We show that eEF2K enhances the accuracy of protein synthesis under a range of conditions and in several cell types. For example, our data reveal it links mammalian (m)TORC1 signaling to the accuracy of translation. Activation of eEF2K decreases misreading or termination readthrough errors during elongation, whereas knocking down or knocking out eEF2K increases their frequency. eEF2K also promotes the correct recognition of start codons in mRNAs. Reduced translational fidelity is known to correlate with shorter lifespan. Consistent with this, deletion of the eEF2K ortholog or other factors implicated in translation fidelity in Caenorhabditis elegans decreases lifespan, and eEF2K is required for lifespan extension induced by nutrient restriction. Our data uncover a novel mechanism linking nutrient supply, mTORC1 signaling, and the elongation stage of protein synthesis, which enhances the accuracy of protein synthesis. Our data also indicate that modulating translation elongation and its fidelity affects lifespan.

Published
2019

41. Comparative Evaluation of Enteric Bacterial Culture and a Molecular Multiplex Syndromic Panel in Children with Acute Gastroenteritis

Author

Kellner, Thomas, primary, Parsons, Brendon, additional, Chui, Linda, additional, Berenger, Byron M., additional, Xie, Jianling, additional, Burnham, Carey-Ann D., additional, Tarr, Phillip I., additional, Lee, Bonita E., additional, Nettel-Aguirre, Alberto, additional, Szelewicki, Jonas, additional, Vanderkooi, Otto G., additional, Pang, Xiao-Li, additional, Zelyas, Nathan, additional, and Freedman, Stephen B., additional

Published
2019
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42. Pigment Visibility on Rectal Swabs Used To Detect Enteropathogens: a Prospective Cohort Study

Author

Xie, Jianling, primary, Tarr, Gillian A. M., additional, Ali, Samina, additional, Chui, Linda, additional, Pang, Xiao-Li, additional, Lee, Bonita E., additional, Vanderkooi, Otto G., additional, Tarr, Phillip I., additional, Zhuo, Ran, additional, Parsons, Brendon, additional, Berenger, Byron M., additional, Kim, Kelly, additional, and Freedman, Stephen B., additional

Published
2019
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45. A randomized trial evaluating virus-specific effects of a combination probiotic in children with acute gastroenteritis.

Author

Freedman, Stephen B., Xie, Jianling, Nettel-Aguirre, Alberto, Pang, Xiao-Li, Chui, Linda, Williamson-Urquhart, Sarah, Schnadower, David, Schuh, Suzanne, Sherman, Philip M., Lee, Bonita E., Gouin, Serge, Farion, Ken J., Poonai, Naveen, Hurley, Katrina F., Qiu, Yuanyuan, Ghandi, Binal, Lloyd, Colin, Finkelstein, Yaron, the Pediatric Emergency Research Canada Probiotic (PERC) Regimen for Outpatient Gastroenteritis Utility of Treatment (PROGUT) Trial Group, and Lee, Bonita

Subjects
ROTAVIRUSES, NOROVIRUS diseases, LACTOBACILLUS rhamnosus, ROTAVIRUS vaccines, GASTROENTERITIS, CHILD death, NUCLEIC acids
Abstract

Gastroenteritis accounts for nearly 500,000 deaths in children younger than 5 years annually. Although probiotics have been touted as having the potential to expedite diarrhea resolution, recent clinical trials question their effectiveness. A potential explanation is a shift in pathogens following the introduction of a rotavirus vaccine. Here, we report the results of a multi-center, double-blind trial of 816 children with acute gastroenteritis who completed follow-up and provided multiple stool specimens. Participants were randomized to receive a probiotic containing Lactobacillus rhamnosus and Lactobacillushelveticus or placebo. We report no virus-specific beneficial effects attributable to the probiotic, either in reducing clinical symptoms or viral nucleic acid clearance from stool specimens collected up to 28 days following enrollment. We provide pathophysiological and microbiologic evidence to support the clinical findings and conclude that our data do not support routine probiotic administration to children with acute gastroenteritis, regardless of the infecting virus. Here, the authors report the results of a randomized, placebo controlled trial of children with acute gastroenteritis who were treated with a probiotic and find no virus-specific beneficial effects attributable to the probiotic, either in reducing clinical symptoms or clearance of viral nucleic acid from stool specimens. [ABSTRACT FROM AUTHOR]

Published
2020
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46. Post–COVID-19 Condition in Children 6 and 12 Months After Infection.

Author

Dun-Dery, Frederick, Xie, Jianling, Winston, Kathleen, Burstein, Brett, Gravel, Jocelyn, Emsley, Jason, Sabhaney, Vikram, Zemek, Roger, Berthelot, Simon, Beer, Darcy, Kam, April, Freire, Gabrielle, Mater, Ahmed, Porter, Robert, Poonai, Naveen, Moffatt, Anne, Dixon, Andrew, Salvadori, Marina I., and Freedman, Stephen B.

Published
2023
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50. mTORC1 Plays an Important Role in Skeletal Development by Controlling Preosteoblast Differentiation

Author

Fitter, Stephen, primary, Matthews, Mary P., additional, Martin, Sally K., additional, Xie, Jianling, additional, Ooi, Soo Siang, additional, Walkley, Carl R., additional, Codrington, John D., additional, Ruegg, Markus A., additional, Hall, Michael N., additional, Proud, Christopher G., additional, Gronthos, Stan, additional, and Zannettino, Andrew C. W., additional

Published
2017
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