Pub Date : 2024-03-15DOI: 10.1101/2024.03.11.24304090
Michaela Ruttorf, Julia Filip, Thomas Schaible, Meike Weis, Frank G Zoellner
School-aged and adolescent survivors of neonatal extracorporeal membrane oxygenation (ECMO) treatment still suffer from neurodevelopmental delays such as verbal, visuo-spatial and working memory problems, motor dysfunction and sensorineural hearing loss, respectively, later in life. These neurodevelopmental delays are normally assessed by neuropsychological testing within follow-up programs. The purpose of this study is to demonstrate that diffusion-weighted imaging (DWI) in 2-year-old survivors of neonatal ECMO treatment might be a predictor of neurodevelopmental outcome. Therefore, 56 children underwent DWI at 3 T. Fractional anisotropy (FA), first fibre partial volume fraction estimate (F1) and radial diffusivity (RD) are compared using tract-based spatial statistics adapted to a paediatric brain atlas and whole-brain voxelwise statistics with age and gender as covariates of no interest. A significant difference in FA, F1 and RD between no-ECMO and ECMO group is seen in major white matter tracts and subcortical white matter in gyri leading to the conclusion that these differences are driven by alterations in axon coherence. Additionally, we examine individual diffusion measures by looking at masks from 50 brain regions taken from a paediatric brain atlas. We find left anterior corona radiata, left and right corpus callosum (genu, body and splenium), left and right crus of fornix, left anterior limb of internal capsule, left anterior commissure, left tapetum and right uncinate fasciculus to have significantly different means in no-ECMO compared to ECMO group which matches the reports of neuropsychological delays found in behavioural tests. To conclude, analysing diffusion measures at an early stage of life serves as a good tool to detect structural white matter changes in survivors of neonatal ECMO treatment like lacking axon coherence in fibre bundles which develop early in life. The advantage of DWI lies in looking only at the neurobiology, e.g. white matter integrity. Compared to neuropsychological testing, DWI in this age range is a very time-efficient method which does not depend on the child's active participation. Additional targeted training could help to mitigate the neurodevelopmental deficits ECMO survivors face later in life.
{"title":"White Matter Integrity Differences in 2-year-old Children Treated with ECMO: A Diffusion-Weighted Imaging Study","authors":"Michaela Ruttorf, Julia Filip, Thomas Schaible, Meike Weis, Frank G Zoellner","doi":"10.1101/2024.03.11.24304090","DOIUrl":"https://doi.org/10.1101/2024.03.11.24304090","url":null,"abstract":"School-aged and adolescent survivors of neonatal extracorporeal membrane oxygenation (ECMO) treatment still suffer from neurodevelopmental delays such as verbal, visuo-spatial and working memory problems, motor dysfunction and sensorineural hearing loss, respectively, later in life. These neurodevelopmental delays are normally assessed by neuropsychological testing within follow-up programs. The purpose of this study is to demonstrate that diffusion-weighted imaging (DWI) in 2-year-old survivors of neonatal ECMO treatment might be a predictor of neurodevelopmental outcome. Therefore, 56 children underwent DWI at 3 T. Fractional anisotropy (FA), first fibre partial volume fraction estimate (F1) and radial diffusivity (RD) are compared using tract-based spatial statistics adapted to a paediatric brain atlas and whole-brain voxelwise statistics with age and gender as covariates of no interest. A significant difference in FA, F1 and RD between no-ECMO and ECMO group is seen in major white matter tracts and subcortical white matter in gyri leading to the conclusion that these differences are driven by alterations in axon coherence. Additionally, we examine individual diffusion measures by looking at masks from 50 brain regions taken from a paediatric brain atlas. We find left anterior corona radiata, left and right corpus callosum (genu, body and splenium), left and right crus of fornix, left anterior limb of internal capsule, left anterior commissure, left tapetum and right uncinate fasciculus to have significantly different means in no-ECMO compared to ECMO group which matches the reports of neuropsychological delays found in behavioural tests. To conclude, analysing diffusion measures at an early stage of life serves as a good tool to detect structural white matter changes in survivors of neonatal ECMO treatment like lacking axon coherence in fibre bundles which develop early in life. The advantage of DWI lies in looking only at the neurobiology, e.g. white matter integrity. Compared to neuropsychological testing, DWI in this age range is a very time-efficient method which does not depend on the child's active participation. Additional targeted training could help to mitigate the neurodevelopmental deficits ECMO survivors face later in life.","PeriodicalId":501549,"journal":{"name":"medRxiv - Pediatrics","volume":"16 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140148191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-13DOI: 10.1101/2024.03.08.24303999
Jeanne Moor, Nicole Toepfner, Wolfgang C. G. von Meissner, Reinhard Berner, Matthias B. Moor, Karolina Kublickiene, Christoph Strumann, Cho-Ming Chao
Background Sex differences exist not only in the efficacy but also in adverse event rates of many vaccines. Here we compared the safety of BNT162b2 vaccine administered off-label in female and male children younger than 5 years in Germany. Methods This is a retrospective cohort study, in which we performed a post-hoc analysis of a dataset collected through an authentication-based survey of individuals having registered children aged 0-<5 years for vaccination against SARS-CoV-2 in six private practices and/or two lay person-initiated vaccination campaigns. We analyzed the safety profiles of the first 3 doses of 3-10μg BNT162b2. Primary outcome was comparison in frequencies of 4 common post-vaccination symptom categories such as local, general, musculoskeletal symptoms and fever. Data were analyzed according to sex in bivariate analyses and regression models adjusting for age, weight, and dosage. Interaction between sex and BNT162b2 dosage was assessed. An active-comparator analysis was applied to compare post-vaccination symptoms after BNT162b2 versus non-SARS-CoV-2 vaccines. Results The dataset for the present analysis consisted of 7801 participants including 3842 females (49%) and 3977 males (51%) with an age of 3 years (median, interquartile: 2 years). Among individuals receiving 3μg BNT162b2, no sex differences were noted, but after a first dose of 5 or 10μg BNT162b2, local injection-site symptoms were more prevalent in girls compared to boys. In logistic regression, female sex was associated with higher odds of local symptoms, odds ratio (OR) of 1.33 (95% confidence interval [CI]: 1.15-1.55, p<0.05) and general symptoms with OR 1.21 (95% CI: 1.01-1.44, p<0.05). Following non-BNT162b2 childhood vaccinations, female sex was associated with a lower odds of post-vaccination musculoskeletal symptoms (OR: 0.29, 95% CI: 0.11-0.82, p<0.05). An active comparator analysis between BNT162b2 and non-SARS-CoV-2 vaccinations revealed that female sex positively influenced the association between BNT162b2 vaccine type and musculoskeletal symptoms. Conclusions Sex differences exist in post-vaccination symptoms after BNT162b2 administration even in young children. These are of importance for the conception of approval studies, for post-vaccination monitoring and for future vaccination strategies. (German Clinical Trials Register ID: DRKS00028759).
{"title":"Sex differences in symptoms following the administration of BNT162b2 mRNA Covid-19 Vaccine in Children below 5 Years of age in Germany (CoVacU5): a retrospective cohort study","authors":"Jeanne Moor, Nicole Toepfner, Wolfgang C. G. von Meissner, Reinhard Berner, Matthias B. Moor, Karolina Kublickiene, Christoph Strumann, Cho-Ming Chao","doi":"10.1101/2024.03.08.24303999","DOIUrl":"https://doi.org/10.1101/2024.03.08.24303999","url":null,"abstract":"Background\u0000Sex differences exist not only in the efficacy but also in adverse event rates of many vaccines. Here we compared the safety of BNT162b2 vaccine administered off-label in female and male children younger than 5 years in Germany. Methods\u0000This is a retrospective cohort study, in which we performed a post-hoc analysis of a dataset collected through an authentication-based survey of individuals having registered children aged 0-<5 years for vaccination against SARS-CoV-2 in six private practices and/or two lay person-initiated vaccination campaigns. We analyzed the safety profiles of the first 3 doses of 3-10μg BNT162b2. Primary outcome was comparison in frequencies of 4 common post-vaccination symptom categories such as local, general, musculoskeletal symptoms and fever. Data were analyzed according to sex in bivariate analyses and regression models adjusting for age, weight, and dosage. Interaction between sex and BNT162b2 dosage was assessed. An active-comparator analysis was applied to compare post-vaccination symptoms after BNT162b2 versus non-SARS-CoV-2 vaccines. Results\u0000The dataset for the present analysis consisted of 7801 participants including 3842 females (49%) and 3977 males (51%) with an age of 3 years (median, interquartile: 2 years). Among individuals receiving 3μg BNT162b2, no sex differences were noted, but after a first dose of 5 or 10μg BNT162b2, local injection-site symptoms were more prevalent in girls compared to boys. In logistic regression, female sex was associated with higher odds of local symptoms, odds ratio (OR) of 1.33 (95% confidence interval [CI]: 1.15-1.55, p<0.05) and general symptoms with OR 1.21 (95% CI: 1.01-1.44, p<0.05). Following non-BNT162b2 childhood vaccinations, female sex was associated with a lower odds of post-vaccination musculoskeletal symptoms (OR: 0.29, 95% CI: 0.11-0.82, p<0.05). An active comparator analysis between BNT162b2 and non-SARS-CoV-2 vaccinations revealed that female sex positively influenced the association between BNT162b2 vaccine type and musculoskeletal symptoms. Conclusions\u0000Sex differences exist in post-vaccination symptoms after BNT162b2 administration even in young children. These are of importance for the conception of approval studies, for post-vaccination monitoring and for future vaccination strategies.\u0000(German Clinical Trials Register ID: DRKS00028759).","PeriodicalId":501549,"journal":{"name":"medRxiv - Pediatrics","volume":"44 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140125807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-08DOI: 10.1101/2024.03.06.24303645
Conor J Loy, Venice Servellita, Alicia Sotomayor-Gonzalez, Andrew Bliss, Joan Lenz, Emma Belcher, Will Suslovic, Jenny Nguyen, Meagan Williams, Miriam Oseguera, Michael Gardiner, Pediatric Emergency Medicine Kawasaki Disease Research Group (PEMKDRG), The CHARMS Study Group, Jong-Ha Choi, Hui-Mien Hsiao, Hao Wang, Jihoon Kim, Chisato Shimizu, Adrianna Tremoulet, Meghan Delaney, Roberta DeBiasi, Christina Rostad, Jane Burns, Charles Chiu, Iwijn De Vlaminck
Inflammatory syndromes, including those caused by infection, are a major cause of hospital admissions among children and are often misdiagnosed because of a lack of advanced molecular diagnostic tools. In this study, we explored the utility of circulating cell-free RNA (cfRNA) in plasma as an analyte for the differential diagnosis and characterization of pediatric inflammatory syndromes. We profiled cfRNA in 370 plasma samples from pediatric patients with a range of inflammatory conditions, including Kawasaki disease (KD), Multisystem Inflammatory Syndrome in Children (MIS-C), viral infections and bacterial infections. We developed machine learning models based on these cfRNA profiles, which effectively differentiated KD from MIS-C - two conditions presenting with overlapping symptoms - with high performance (Test Area Under the Curve (AUC) = 0.97). We further extended this methodology into a multiclass machine learning framework that achieved 81% accuracy in distinguishing among KD, MIS-C, viral, and bacterial infections. We further demonstrated that cfRNA profiles can be used to quantify injury to specific tissues and organs, including the liver, heart, endothelium, nervous system, and the upper respiratory tract. Overall, this study identified cfRNA as a versatile analyte for the differential diagnosis and characterization of a wide range of pediatric inflammatory syndromes.
{"title":"Plasma Cell-free RNA Signatures of Inflammatory Syndromes in Children","authors":"Conor J Loy, Venice Servellita, Alicia Sotomayor-Gonzalez, Andrew Bliss, Joan Lenz, Emma Belcher, Will Suslovic, Jenny Nguyen, Meagan Williams, Miriam Oseguera, Michael Gardiner, Pediatric Emergency Medicine Kawasaki Disease Research Group (PEMKDRG), The CHARMS Study Group, Jong-Ha Choi, Hui-Mien Hsiao, Hao Wang, Jihoon Kim, Chisato Shimizu, Adrianna Tremoulet, Meghan Delaney, Roberta DeBiasi, Christina Rostad, Jane Burns, Charles Chiu, Iwijn De Vlaminck","doi":"10.1101/2024.03.06.24303645","DOIUrl":"https://doi.org/10.1101/2024.03.06.24303645","url":null,"abstract":"Inflammatory syndromes, including those caused by infection, are a major cause of hospital admissions among children and are often misdiagnosed because of a lack of advanced molecular diagnostic tools. In this study, we explored the utility of circulating cell-free RNA (cfRNA) in plasma as an analyte for the differential diagnosis and characterization of pediatric inflammatory syndromes. We profiled cfRNA in 370 plasma samples from pediatric patients with a range of inflammatory conditions, including Kawasaki disease (KD), Multisystem Inflammatory Syndrome in Children (MIS-C), viral infections and bacterial infections. We developed machine learning models based on these cfRNA profiles, which effectively differentiated KD from MIS-C - two conditions presenting with overlapping symptoms - with high performance (Test Area Under the Curve (AUC) = 0.97). We further extended this methodology into a multiclass machine learning framework that achieved 81% accuracy in distinguishing among KD, MIS-C, viral, and bacterial infections. We further demonstrated that cfRNA profiles can be used to quantify injury to specific tissues and organs, including the liver, heart, endothelium, nervous system, and the upper respiratory tract. Overall, this study identified cfRNA as a versatile analyte for the differential diagnosis and characterization of a wide range of pediatric inflammatory syndromes.","PeriodicalId":501549,"journal":{"name":"medRxiv - Pediatrics","volume":"17 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140071924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-08DOI: 10.1101/2024.03.07.24303907
David Lyle George Horner, Jens Richardt moellegaard Jepsen, Bo Chawes, Kristin Aagaard, Julie Rosenberg, Parisa Mohammadzadeh, Astrid Sevelsted, Nilo Vahman, Rebecca Vinding, Birgitte Fagerlund, Christos Pantelis, Niels Bilenberg, Casper-Emil Pedersen, Anders Eliasen, Yulu Chen, Nicole Prince, Su Chu, Rachel Kelly, Jessica Lasky-Su, Thorhallur Halldorsson, Birte Glenthooj, Klaus Boonelykke, Bjoern Ebdrup, Jakob Stokholm, Morten Arendt Rasmussen
Despite the high prevalence of neurodevelopmental disorders, there are a lack of clinical studies examining the impact of pregnancy diet on child neurodevelopment. This observational clinical study examined the associations between pregnancy dietary patterns and neurodevelopmental diagnoses, as well as their symptoms, in a prospective cohort of 10-year-old children (n=508). Data-driven dietary patterns were derived from self-reported food frequency questionnaires. An Unhealthy dietary pattern in pregnancy (per SD change) was significantly associated with attention deficit hyperactivity disorder (ADHD) OR 1.66 [1.21 - 2.27], p=0.002 and autism diagnosis OR 2.22 [1.33 - 3.74], p=0.002 and associated symptoms p<0.001. Findings for ADHD were validated in two large (n=656, n=348), independent mother-child cohorts via blood metabolome modelling. Objective metabolite scores, assessed at five timepoints in mothers and children in two independent mother-child cohorts, indicated that the strongest association with ADHD was during early- to mid- pregnancy. These results provide evidence for targeted prenatal dietary interventions to prevent neurodevelopmental disorders in children.
{"title":"An Unhealthy Dietary Pattern during Pregnancy is Associated with Neurodevelopmental Disorders in Childhood and Adolescence","authors":"David Lyle George Horner, Jens Richardt moellegaard Jepsen, Bo Chawes, Kristin Aagaard, Julie Rosenberg, Parisa Mohammadzadeh, Astrid Sevelsted, Nilo Vahman, Rebecca Vinding, Birgitte Fagerlund, Christos Pantelis, Niels Bilenberg, Casper-Emil Pedersen, Anders Eliasen, Yulu Chen, Nicole Prince, Su Chu, Rachel Kelly, Jessica Lasky-Su, Thorhallur Halldorsson, Birte Glenthooj, Klaus Boonelykke, Bjoern Ebdrup, Jakob Stokholm, Morten Arendt Rasmussen","doi":"10.1101/2024.03.07.24303907","DOIUrl":"https://doi.org/10.1101/2024.03.07.24303907","url":null,"abstract":"Despite the high prevalence of neurodevelopmental disorders, there are a lack of clinical studies examining the impact of pregnancy diet on child neurodevelopment. This observational clinical study examined the associations between pregnancy dietary patterns and neurodevelopmental diagnoses, as well as their symptoms, in a prospective cohort of 10-year-old children (n=508). Data-driven dietary patterns were derived from self-reported food frequency questionnaires. An Unhealthy dietary pattern in pregnancy (per SD change) was significantly associated with attention deficit hyperactivity disorder (ADHD) OR 1.66 [1.21 - 2.27], p=0.002 and autism diagnosis OR 2.22 [1.33 - 3.74], p=0.002 and associated symptoms p<0.001. Findings for ADHD were validated in two large (n=656, n=348), independent mother-child cohorts via blood metabolome modelling. Objective metabolite scores, assessed at five timepoints in mothers and children in two independent mother-child cohorts, indicated that the strongest association with ADHD was during early- to mid- pregnancy. These results provide evidence for targeted prenatal dietary interventions to prevent neurodevelopmental disorders in children.","PeriodicalId":501549,"journal":{"name":"medRxiv - Pediatrics","volume":"40 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140072024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-07DOI: 10.1101/2024.03.05.24303778
Nora Bruns, Nadia Feddahi, Rayan Hojeij, Rainer Rossi, Christian Dohna-Schwake, Anja Stein, Susann Kobus, Andreas Stang, Bernd Kowall, Ursula Felderhoff-Mueser
Importance: In neonates with birth asphyxia (BA) and hypoxic ischemic encephalopathy, therapeutic hypothermia (TH), initiated within six hours, is the only safe and established neuroprotective measure to prevent secondary brain injury. Infants born outside of TH centers have delayed access to cooling. Objective: To compare in-hospital lethality, occurrence of seizures, and functional status at discharge in newborns with BA depending on postnatal transfer to another hospital within 24 hours of admission (outborn versus inborn). Design: Nationwide retrospective cohort study from a comprehensive hospital dataset using codes of the International Classification of Diseases, 10th modification (ICD-10). Clinical and outcome information was retrieved from diagnostic and procedural codes. Hierarchical multilevel logistic regression modelling was performed to quantify the effect of being outborn on target outcomes. Setting: All admissions to German hospitals 2016 - 2021. Participants: Full term neonates with birth asphyxia (ICD-10 code: P21) admitted to a pediatric department on their first day of life. Exposures: Transfer to a pediatric department within 24 hours of admission to an external hospital (=outborn). Main outcomes: In-hospital death; secondary outcomes: seizures and pediatric complex chronic conditions category (PCCC) >= 2. Results: Of 11,703,800 pediatric cases, 25,914 fulfilled the inclusion criteria. Outborns had higher proportions of organ dysfunction, TH, organ replacement therapies, and neurological sequelae in spite of slightly lower proportions of maternal risk factors. The adjusted odds ratios (OR) for death, seizures, and PCCC >= 2 were 4.08 ((95 % confidence interval 3.41 - 4.89), 2.99 (2.65 - 3.38), and 1.76 (1.52 - 2.05), respectively, if infants were outborn compared to inborn. A subgroup analysis among infants receiving TH (n = 3,283) found less pronounced adjusted ORs for death (1.67 (1.29 - 2.17)) and seizures (1.26 (1.07 - 1.48)) and inversed effects for PCCC >= 2 (0.81 (0.64 - 1.02)). Conclusion and relevance: This comprehensive nationwide study found increased odds for adverse outcomes in neonates with BA who were transferred to another facility within 24 hours of hospital admission. Obstetrical units should be linked to a pediatric department to minimize risks of postnatal emergency transfer. Collaboration and coordination between centers should be improved to balance geographical coverage of different level care facilities.
{"title":"Short-term outcomes of asphyxiated neonates depending on outborn versus inborn status","authors":"Nora Bruns, Nadia Feddahi, Rayan Hojeij, Rainer Rossi, Christian Dohna-Schwake, Anja Stein, Susann Kobus, Andreas Stang, Bernd Kowall, Ursula Felderhoff-Mueser","doi":"10.1101/2024.03.05.24303778","DOIUrl":"https://doi.org/10.1101/2024.03.05.24303778","url":null,"abstract":"Importance: In neonates with birth asphyxia (BA) and hypoxic ischemic encephalopathy, therapeutic hypothermia (TH), initiated within six hours, is the only safe and established neuroprotective measure to prevent secondary brain injury. Infants born outside of TH centers have delayed access to cooling.\u0000Objective: To compare in-hospital lethality, occurrence of seizures, and functional status at discharge in newborns with BA depending on postnatal transfer to another hospital within 24 hours of admission (outborn versus inborn). Design: Nationwide retrospective cohort study from a comprehensive hospital dataset using codes of the International Classification of Diseases, 10th modification (ICD-10). Clinical and outcome information was retrieved from diagnostic and procedural codes. Hierarchical multilevel logistic regression modelling was performed to quantify the effect of being outborn on target outcomes.\u0000Setting: All admissions to German hospitals 2016 - 2021. Participants: Full term neonates with birth asphyxia (ICD-10 code: P21) admitted to a pediatric department on their first day of life.\u0000Exposures: Transfer to a pediatric department within 24 hours of admission to an external hospital (=outborn).\u0000Main outcomes: In-hospital death; secondary outcomes: seizures and pediatric complex chronic conditions category (PCCC) >= 2. Results: Of 11,703,800 pediatric cases, 25,914 fulfilled the inclusion criteria. Outborns had higher proportions of organ dysfunction, TH, organ replacement therapies, and neurological sequelae in spite of slightly lower proportions of maternal risk factors. The adjusted odds ratios (OR) for death, seizures, and PCCC >= 2 were 4.08 ((95 % confidence interval 3.41 - 4.89), 2.99 (2.65 - 3.38), and 1.76 (1.52 - 2.05), respectively, if infants were outborn compared to inborn. A subgroup analysis among infants receiving TH (n = 3,283) found less pronounced adjusted ORs for death (1.67 (1.29 - 2.17)) and seizures (1.26 (1.07 - 1.48)) and inversed effects for PCCC >= 2 (0.81 (0.64 - 1.02)). Conclusion and relevance: This comprehensive nationwide study found increased odds for adverse outcomes in neonates with BA who were transferred to another facility within 24 hours of hospital admission. Obstetrical units should be linked to a pediatric department to minimize risks of postnatal emergency transfer. Collaboration and coordination between centers should be improved to balance geographical coverage of different level care facilities.","PeriodicalId":501549,"journal":{"name":"medRxiv - Pediatrics","volume":"30 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140055933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by persistent deficits in social communication and interaction, along with restricted and repetitive behaviour patterns, interests or activities. Its prevalence has risen over the past few years, being four times more common in boys than girls. The cause of ASD is unclear, its etiology involves genetic, environmental, and gene-environment interactions. While past studies highlighted clinical genetic risks, genetic complexity of ASD, with variants of diverse frequencies, type, and inheritance patterns, requires further exploration for better management of disease. Researches have shown that the whole exome sequencing can be used to identify genetic variants associated with genetically heterogeneous conditions. The purpose of this study is to identify genetic variants by employing whole exome sequencing in an Indian ASD patient. Methods: A female patient of age within 0-5 years, having characteristic features like hyperactivity and language impairment, was investigated and diagnosed using DSM-5 criteria. Peripheral blood sample collection was done followed by DNA extraction and whole exome sequencing. Variants analysis, identification and annotation were done using bioinformatics tools and databases. Identified pathogenic variants were reconfirmed by Sanger sequencing. Results and conclusion: Our study uncover four genetic variations, comprising three missense variations in KIF1A (c.3839C>T), SETD5 (c.314A>C), MAPK81P3 (c.2849C>T), and one-stop gain variation in ERMARD (c.1523G>A). The ERMARD stop gain variation, predicted to induce nonsense-mediated decay, alter normal protein function through truncation and classified as likely pathogenic based on the ACMG guidelines and current available scientific evidence. In conclusion, we identified a likely pathogenic variant in ERMARD along with three missense variants in KIF1A, SETD5 and MAPK81P3 respectively. These findings suggest the potential contribution of ERMARD mutations to ASD susceptibility, emphasizing the need for further validation through functional studies. Keywords: Autism spectrum disorder, neurodevelopmental disorder, whole exome sequencing, language impairment, bioinformatics, missense variation
{"title":"Identification of Novel Gene variants for Autism Spectrum Disorder in an Indian Patient using Whole Exome Sequencing","authors":"Prashasti Yadav, Saileyee Roychowdhury, Nilanjan Mukherjee, Reema Mukherjee, Sudipta Kumar Roy, Soumen Bhattacharjee, Parimal Das","doi":"10.1101/2024.02.28.24303417","DOIUrl":"https://doi.org/10.1101/2024.02.28.24303417","url":null,"abstract":"Background: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by persistent deficits in social communication and interaction, along with restricted and repetitive behaviour patterns, interests or activities. Its prevalence has risen over the past few years, being four times more common in boys than girls. The cause of ASD is unclear, its etiology involves genetic, environmental, and gene-environment interactions. While past studies highlighted clinical genetic risks, genetic complexity of ASD, with variants of diverse frequencies, type, and inheritance patterns, requires further exploration for better management of disease. Researches have shown that the whole exome sequencing can be used to identify genetic variants associated with genetically heterogeneous conditions. The purpose of this study is to identify genetic variants by employing whole exome sequencing in an Indian ASD patient.\u0000Methods: A female patient of age within 0-5 years, having characteristic features like hyperactivity and language impairment, was investigated and diagnosed using DSM-5 criteria. Peripheral blood sample collection was done followed by DNA extraction and whole exome sequencing. Variants analysis, identification and annotation were done using bioinformatics tools and databases. Identified pathogenic variants were reconfirmed by Sanger sequencing.\u0000Results and conclusion: Our study uncover four genetic variations, comprising three missense variations in KIF1A (c.3839C>T), SETD5 (c.314A>C), MAPK81P3 (c.2849C>T), and one-stop gain variation in ERMARD (c.1523G>A). The ERMARD stop gain variation, predicted to induce nonsense-mediated decay, alter normal protein function through truncation and classified as likely pathogenic based on the ACMG guidelines and current available scientific evidence. In conclusion, we identified a likely pathogenic variant in ERMARD along with three missense variants in KIF1A, SETD5 and MAPK81P3 respectively. These findings suggest the potential contribution of ERMARD mutations to ASD susceptibility, emphasizing the need for further validation through functional studies. Keywords: Autism spectrum disorder, neurodevelopmental disorder, whole exome sequencing, language impairment, bioinformatics, missense variation","PeriodicalId":501549,"journal":{"name":"medRxiv - Pediatrics","volume":"45 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140020173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-29DOI: 10.1101/2024.02.29.24303539
Sarah R Haile, Gabriela P Peralta, Mark Adams, Ajay N Bharadwaj, Dirk Bassler, Alexander Moeller, Giancarlo Natalucci, Thomas Radtke, Susi Kriemler
Objectives: We aimed to assess health-related quality of life (HRQOL) in a cohort of very preterm born children and adolescents (aged 5-16), and to compare it with their fullterm born siblings and the general population. We also explored correlates of HRQOL among the very preterm born. Methods: Cross-sectional survey. Primary outcome was KINDL total score (0 worst - 100 best). Linear mixed models accounted for family unit. Secondary analysis compared very preterm born children to another cohort of healthy children from the same time period. A classification tree analysis explored potential correlates of HRQOL. Results: On average, preterm children had a 2.1 point lower KINDL total score than fullterm sibling controls (95% CI -3.6 to -0.6). Compared to population controls, very preterm born children had a 1.4 point higher KINDL score (0.2 to 2.5). Chronic health conditions, age, and respiratory symptoms affecting daily life were key correlates of HRQOL among very preterm born children. Conclusions: Very preterm birth in children and adolescents was not associated with a relevant reduction in HRQOL compared to their fullterm born peers. However, lower HRQOL was likely explained by other factors, such as older age, the presence of chronic health conditions, but also by current respiratory symptoms that may be modifiable. A comprehensive assessment of the pulmonary sequelae provoking symptoms and interventions targeting medical management, physical activity and exercise capacity of preterm born children and adolescents may help to reduce respiratory symptoms and its potential influence on HRQOL needs to be investigated further.
{"title":"Health-related quality of life in children and adolescents born very preterm and its correlates","authors":"Sarah R Haile, Gabriela P Peralta, Mark Adams, Ajay N Bharadwaj, Dirk Bassler, Alexander Moeller, Giancarlo Natalucci, Thomas Radtke, Susi Kriemler","doi":"10.1101/2024.02.29.24303539","DOIUrl":"https://doi.org/10.1101/2024.02.29.24303539","url":null,"abstract":"Objectives: We aimed to assess health-related quality of life (HRQOL) in a cohort of very preterm born children and adolescents (aged 5-16), and to compare it with their fullterm born siblings and the general population. We also explored correlates of HRQOL among the very preterm born. Methods: Cross-sectional survey. Primary outcome was KINDL total score (0 worst - 100 best). Linear mixed models accounted for family unit. Secondary analysis compared very preterm born children to another cohort of healthy children from the same time period. A classification tree analysis explored potential correlates of HRQOL. Results: On average, preterm children had a 2.1 point lower KINDL total score than fullterm sibling controls (95% CI -3.6 to -0.6). Compared to population controls, very preterm born children had a 1.4 point higher KINDL score (0.2 to 2.5). Chronic health conditions, age, and respiratory symptoms affecting daily life were key correlates of HRQOL among very preterm born children. Conclusions: Very preterm birth in children and adolescents was not associated with a relevant reduction in HRQOL compared to their fullterm born peers. However, lower HRQOL was likely explained by other factors, such as older age, the presence of chronic health conditions, but also by current respiratory symptoms that may be modifiable. A comprehensive assessment of the pulmonary sequelae provoking symptoms and interventions targeting medical management, physical activity and exercise capacity of preterm born children and adolescents may help to reduce respiratory symptoms and its potential influence on HRQOL needs to be investigated further.","PeriodicalId":501549,"journal":{"name":"medRxiv - Pediatrics","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140005178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-23DOI: 10.1101/2024.02.22.24303209
Oguzhan Serin, Izzet Turkalp Akbasli, Sena Bocutcu Cetin, Busra Koseoglu, Ahmet Fatih Deveci, Muhsin Zahid Ugur, Yasemin Ozsurekci
Background: Pneumonia is the leading cause of preventable mortality under five years of age. Appropriate case management is as essential as disease prevention interventions, especially in primary care settings. Computer science has been used accurately and widely for pneumonia diagnosis; however, prognosis studies are relatively low. Herein, we developed a machine learning-based clinical decision support system tool for childhood pneumonia to provide prognostic support for case management. Methods: We analyzed data from 437 children admitted to our clinic with a pneumonia diagnosis between 2014 and 2020. Pediatricians encoded the raw dataset according to candidate features. Before the experimental study of the machine learning algorithms of Pycaret, SMOTE-Tomek was utilized for managing imbalanced datasets. The feature selection was made by examining the SHAP values of the algorithm with the highest performance and re-modeled with the most important clinical features. We optimized hyperparameters and employed ensemble methods to develop a robust predictive model. Results: Optimized models predicted pneumonia prognosis with %77-88 accuracy. It was shown that severity could be determined over %84 by five clinical features: hypoxia, respiratory distress, age, Z score of weight for age, and antibiotic usage before admission. Conclusions: In this experimental study, we demonstrated that contemporary data science methods, such as oversampling, feature selection, and machine learning tools, are promising in predicting the critical care need of patients. Even in small-size samples like our study, ML methods can reach current wisdom.
{"title":"Advancing primary care for childhood pneumonia: a machine learning-based approach to prognosis and case management","authors":"Oguzhan Serin, Izzet Turkalp Akbasli, Sena Bocutcu Cetin, Busra Koseoglu, Ahmet Fatih Deveci, Muhsin Zahid Ugur, Yasemin Ozsurekci","doi":"10.1101/2024.02.22.24303209","DOIUrl":"https://doi.org/10.1101/2024.02.22.24303209","url":null,"abstract":"Background: Pneumonia is the leading cause of preventable mortality under five years of age. Appropriate case management is as essential as disease prevention interventions, especially in primary care settings. Computer science has been used accurately and widely for pneumonia diagnosis; however, prognosis studies are relatively low. Herein, we developed a machine learning-based clinical decision support system tool for childhood pneumonia to provide prognostic support for case management.\u0000Methods: We analyzed data from 437 children admitted to our clinic with a pneumonia diagnosis between 2014 and 2020. Pediatricians encoded the raw dataset according to candidate features. Before the experimental study of the machine learning algorithms of Pycaret, SMOTE-Tomek was utilized for managing imbalanced datasets. The feature selection was made by examining the SHAP values of the algorithm with the highest performance and re-modeled with the most important clinical features. We optimized hyperparameters and employed ensemble methods to develop a robust predictive model.\u0000Results: Optimized models predicted pneumonia prognosis with %77-88 accuracy. It was shown that severity could be determined over %84 by five clinical features: hypoxia, respiratory distress, age, Z score of weight for age, and antibiotic usage before admission.\u0000Conclusions: In this experimental study, we demonstrated that contemporary data science methods, such as oversampling, feature selection, and machine learning tools, are promising in predicting the critical care need of patients. Even in small-size samples like our study, ML methods can reach current wisdom.","PeriodicalId":501549,"journal":{"name":"medRxiv - Pediatrics","volume":"30 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139946043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-23DOI: 10.1101/2024.02.21.24303174
Mai-Lei Woo Kinshella, Jean Allen, Jasmine Pawa, Jesse Papenburg, Radha Jetty, Rachel Dwilow, Joan Robinson, Laura Arbour, Manish Sadarangani, Ye Shen, Jeffrey Bone, Michelle Dittrick, Celia Walker, Iryna Kayda, Holden Sheffield, Darcy Scott, Amber Miners, David M Goldfarb
Background: Nunavut is a northern Canadian territory in Inuit Nunangat (Inuit homeland in Canada). Approximately 85% of the population identifies as Inuit. A high proportion of infants in Nunavut are admitted to hospital with acute respiratory tract infection (ARI) but previous studies have been limited in regional and/or short duration of coverage. This study aimed to estimate the incidence rate, microbiology and outcomes of ARI hospitalizations in Nunavut infants. Methods: We conducted chart reviews with a retrospective cohort of infants aged <1 year from Nunavut at six Canadian hospitals, including two regional and four tertiary pediatric hospitals January 1, 2010 to June 30, 2020. Descriptive statistics and multiple logistic regression were performed. Results: We identified 1189 ARI admissions of infants during the study period, with an incidence rate of 133.9 per 1000 infants per year (95% confidence interval (CI): 126.8, 141.3). Of these admissions, 56.0% (n=666) were to regional hospitals alone, 72.3% (n=860) involved hospitalization outside of Nunavut, 15.6% (n=185) were admitted into intensive care, and 9.2% (n=109) underwent mechanical ventilation. Of the 730 admissions with a pathogen identified, 45.8% had respiratory syncytial virus (RSV; n=334), for a yearly incidence rate of 37.8 hospitalizations per 1000 infants (95% CI: 33.9, 42.1). Among RSV hospitalizations, 41.1% (n=138) were infants 0-2 months of age and 32.1% (n=108) were > 6months. Interpretation: Understanding the high burden of ARI among Nunavut infants can inform health policy and serve as a baseline for assessing the impact of any new interventions targeting infant ARIs.
{"title":"Hospital admissions for acute respiratory tract infections among infants from Nunavut and the burden of respiratory syncytial virus: a 10-year review in regional and tertiary hospitals","authors":"Mai-Lei Woo Kinshella, Jean Allen, Jasmine Pawa, Jesse Papenburg, Radha Jetty, Rachel Dwilow, Joan Robinson, Laura Arbour, Manish Sadarangani, Ye Shen, Jeffrey Bone, Michelle Dittrick, Celia Walker, Iryna Kayda, Holden Sheffield, Darcy Scott, Amber Miners, David M Goldfarb","doi":"10.1101/2024.02.21.24303174","DOIUrl":"https://doi.org/10.1101/2024.02.21.24303174","url":null,"abstract":"Background: Nunavut is a northern Canadian territory in Inuit Nunangat (Inuit homeland in Canada). Approximately 85% of the population identifies as Inuit. A high proportion of infants in Nunavut are admitted to hospital with acute respiratory tract infection (ARI) but previous studies have been limited in regional and/or short duration of coverage. This study aimed to estimate the incidence rate, microbiology and outcomes of ARI hospitalizations in Nunavut infants. Methods: We conducted chart reviews with a retrospective cohort of infants aged <1 year from Nunavut at six Canadian hospitals, including two regional and four tertiary pediatric hospitals January 1, 2010 to June 30, 2020. Descriptive statistics and multiple logistic regression were performed. Results: We identified 1189 ARI admissions of infants during the study period, with an incidence rate of 133.9 per 1000 infants per year (95% confidence interval (CI): 126.8, 141.3). Of these admissions, 56.0% (n=666) were to regional hospitals alone, 72.3% (n=860) involved hospitalization outside of Nunavut, 15.6% (n=185) were admitted into intensive care, and 9.2% (n=109) underwent mechanical ventilation. Of the 730 admissions with a pathogen identified, 45.8% had respiratory syncytial virus (RSV; n=334), for a yearly incidence rate of 37.8 hospitalizations per 1000 infants (95% CI: 33.9, 42.1). Among RSV hospitalizations, 41.1% (n=138) were infants 0-2 months of age and 32.1% (n=108) were > 6months. Interpretation: Understanding the high burden of ARI among Nunavut infants can inform health policy and serve as a baseline for assessing the impact of any new interventions targeting infant ARIs.","PeriodicalId":501549,"journal":{"name":"medRxiv - Pediatrics","volume":"70 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139945948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-22DOI: 10.1101/2024.02.20.24302892
Morgan Firestein, Angela Gigliotti Manessis, Jennifer M. Warmingham, Yunzhe Hu, Morgan A. Finkel, Margaret H. Kyle, Maha Hussain, Imaal Ahmed, Andréane Lavallée, Ana Solis, Vitoria Chaves, Cynthia Rodriguez, Sylvie Goldman, Rebecca A. Muhle, Seonjoo Lee, Judy Austin, Wendy G. Silver, Kally C. O'Reilly, Jennifer M. Bain, Anna A. Penn, Jeremy Veenstra-VanderWeele, Melissa S. Stockwell, William P. Fifer, Rachel Marsh, Catherine E. Monk, Lauren C. Shuffrey, Dani Dumitriu
Maternal stress and viral illness during pregnancy are associated with neurodevelopmental conditions in offspring. Children born during the COVID-19 pandemic, including those exposed prenatally to maternal SARS-CoV-2 infections, are reaching the developmental age for the assessment of risk for neurodevelopmental conditions. We examined associations between birth during the COVID-19 pandemic, prenatal exposure to maternal SARS-CoV-2 infection, and rates of positive screenings on the Modified Checklist for Autism in Toddlers-Revised (M-CHAT-R). Data were drawn from the COVID-19 Mother Baby Outcomes (COMBO) Initiative. Participants completed the M-CHAT-R as part of routine clinical care (COMBO-EHR cohort) or for research purposes (COMBO-RSCH cohort). Maternal SARS-CoV-2 status during pregnancy was determined through electronic health records. The COMBO-EHR cohort includes n=1664 children (n=442 historical cohort, n=1222 pandemic cohort; n=997 SARS-CoV-2 unexposed prenatally, n=130 SARS-CoV-2 exposed prenatally) who were born at affiliated hospitals between 2018-2023 and who had a valid M-CHAT-R score in their health record. The COMBO-RSCH cohort consists of n=359 children (n=268 SARS-CoV-2 unexposed prenatally, n=91 SARS-CoV-2 exposed prenatally) born at the same hospitals who enrolled into a prospective cohort study that included administration of the M-CHAT-R at 18-months. Birth during the pandemic was not associated with greater likelihood of a positive M-CHAT-R screen in the COMBO-EHR cohort. Maternal SARS-CoV-2 was associated with lower likelihood of a positive M-CHAT-R screening in adjusted models in the COMBO-EHR cohort (OR=0.40, 95% CI=0.22 - 0.68, p=0.001), while analyses in the COMBO-RSCH cohort yielded similar but non-significant results (OR=0.67, 95% CI=0.31-1.37, p=0.29). These results suggest that children born during the first 18 months of the COVID-19 pandemic and those exposed prenatally to a maternal SARS-CoV-2 infection are not at greater risk for screening positive on the M-CHAT-R.
{"title":"Rates of Positive M-CHAT-R Screenings by Pandemic Birth and Prenatal SARS-CoV-2 Exposure","authors":"Morgan Firestein, Angela Gigliotti Manessis, Jennifer M. Warmingham, Yunzhe Hu, Morgan A. Finkel, Margaret H. Kyle, Maha Hussain, Imaal Ahmed, Andréane Lavallée, Ana Solis, Vitoria Chaves, Cynthia Rodriguez, Sylvie Goldman, Rebecca A. Muhle, Seonjoo Lee, Judy Austin, Wendy G. Silver, Kally C. O'Reilly, Jennifer M. Bain, Anna A. Penn, Jeremy Veenstra-VanderWeele, Melissa S. Stockwell, William P. Fifer, Rachel Marsh, Catherine E. Monk, Lauren C. Shuffrey, Dani Dumitriu","doi":"10.1101/2024.02.20.24302892","DOIUrl":"https://doi.org/10.1101/2024.02.20.24302892","url":null,"abstract":"Maternal stress and viral illness during pregnancy are associated with neurodevelopmental conditions in offspring. Children born during the COVID-19 pandemic, including those exposed prenatally to maternal SARS-CoV-2 infections, are reaching the developmental age for the assessment of risk for neurodevelopmental conditions. We examined associations between birth during the COVID-19 pandemic, prenatal exposure to maternal SARS-CoV-2 infection, and rates of positive screenings on the Modified Checklist for Autism in Toddlers-Revised (M-CHAT-R). Data were drawn from the COVID-19 Mother Baby Outcomes (COMBO) Initiative. Participants completed the M-CHAT-R as part of routine clinical care (COMBO-EHR cohort) or for research purposes (COMBO-RSCH cohort). Maternal SARS-CoV-2 status during pregnancy was determined through electronic health records. The COMBO-EHR cohort includes n=1664 children (n=442 historical cohort, n=1222 pandemic cohort; n=997 SARS-CoV-2 unexposed prenatally, n=130 SARS-CoV-2 exposed prenatally) who were born at affiliated hospitals between 2018-2023 and who had a valid M-CHAT-R score in their health record. The COMBO-RSCH cohort consists of n=359 children (n=268 SARS-CoV-2 unexposed prenatally, n=91 SARS-CoV-2 exposed prenatally) born at the same hospitals who enrolled into a prospective cohort study that included administration of the M-CHAT-R at 18-months. Birth during the pandemic was not associated with greater likelihood of a positive M-CHAT-R screen in the COMBO-EHR cohort. Maternal SARS-CoV-2 was associated with lower likelihood of a positive M-CHAT-R screening in adjusted models in the COMBO-EHR cohort (OR=0.40, 95% CI=0.22 - 0.68, p=0.001), while analyses in the COMBO-RSCH cohort yielded similar but non-significant results (OR=0.67, 95% CI=0.31-1.37, p=0.29). These results suggest that children born during the first 18 months of the COVID-19 pandemic and those exposed prenatally to a maternal SARS-CoV-2 infection are not at greater risk for screening positive on the M-CHAT-R.","PeriodicalId":501549,"journal":{"name":"medRxiv - Pediatrics","volume":"141 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139946268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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