Featured
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| Open AccessInfant gut microbiome composition is associated with non-social fear behavior in a pilot study
Experimental manipulation of the gut microbiome in animal models impacts fear behaviours. Here, the authors show in a pilot study that features of the human infant gut microbiome are associated with non-social fear behaviours during a laboratory based assessment.
- Alexander L. Carlson
- , Kai Xia
- & Rebecca C. Knickmeyer
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| Open AccessAssociation between confirmed congenital Zika infection at birth and outcomes up to 3 years of life
Here, using diagnostic tools in a longitudinal cohort of ZIKV-infected pregnant women of the French Guiana Western Hospital Center (CHOG) and their infants, the authors investigate the long term neuropathological effects of congenital infection, finding that a laboratory confirmed congenital ZIKV infection at birth is associated with higher risks of adverse neurological outcomes up to three years of life.
- Najeh Hcini
- , Yaovi Kugbe
- & Léo Pomar
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| Open AccessEnhanced influenza A H1N1 T cell epitope recognition and cross-reactivity to protein-O-mannosyltransferase 1 in Pandemrix-associated narcolepsy type 1
Narcolepsy type 1 (NT1) is a severe sleep disorder with strong association to the HLA type DQB1*0602 and increased incidence among children vaccinated with the Influenza A vaccine Pandemrix. Here the authors show that these children develop T and B cell autoimmunity against protein-O-mannosyltransferase 1 via cross-reactivity.
- A. Vuorela
- , T. L. Freitag
- & O. Vaarala
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| Open AccessEnsembled deep learning model outperforms human experts in diagnosing biliary atresia from sonographic gallbladder images
It is still challenging to make accurate diagnosis of biliary atresia (BA) with sonographic gallbladder images particularly in rural areas without relevant expertise. Here, the authors develop a diagnostic deep learning model which favourable performance in comparison with human experts in multi-center external validation.
- Wenying Zhou
- , Yang Yang
- & Luyao Zhou
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| Open AccessExposure to pesticides in utero impacts the fetal immune system and response to vaccination in infancy
Control of mosquito populations using pesticides is important for malaria elimination, but effects of pesticides on humans aren’t well understood. Here, Prahl et al. show in a cohort of pregnant Ugandan women and their infants that household spraying with bendiocarb affects the fetal immune system and response to vaccination in infancy.
- Mary Prahl
- , Pamela Odorizzi
- & Margaret E. Feeney
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| Open AccessImmune responses to SARS-CoV-2 in three children of parents with symptomatic COVID-19
Children with SARS-CoV-2 infection are more likely to have mild symptoms and may be asymptomatic, but underlying reasons remain unclear. Here, the authors show cellular, cytokine and antibody response to SARS-CoV-2 infection in three children who repeatedly tested negative for the virus by PCR, despite high exposure in the household.
- Shidan Tosif
- , Melanie R. Neeland
- & Nigel W. Crawford
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| Open AccessSynthesis and systematic review of reported neonatal SARS-CoV-2 infections
There are a growing number of reports of neonatal SARS-CoV-2 infections. Here, De Luca and colleagues systematically analyse 176 published cases to better understand the route of transmission, as well as the clinical features and outcomes of neonatal COVID-19.
- Roberto Raschetti
- , Alexandre J. Vivanti
- & Daniele De Luca
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| Open AccessFetal whole heart blood flow imaging using 4D cine MRI
Three-dimensional imaging of the fetal heart and quantification of blood flow in the surrounding vessels is very challenging because the heart is small and the fetus is free to move in the womb. Here, the authors demonstrate motion-corrected 4D flow MRI of the whole fetal heart and major vessels.
- Thomas A. Roberts
- , Joshua F. P. van Amerom
- & Joseph V. Hajnal
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| Open AccessSerological identification of SARS-CoV-2 infections among children visiting a hospital during the initial Seattle outbreak
COVID-19 disease is less common in children than adults, but the extent to which SARS-CoV-2 infections are missed through symptom-driven testing is not well understood. In this study, the authors show that approximately 1% of children seeking care for reasons other than COVID-19 at a Seattle hospital in March/April 2020 were seropositive for SARS-CoV-2.
- Adam S. Dingens
- , Katharine H. D. Crawford
- & Jesse D. Bloom
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| Open AccessA lung tropic AAV vector improves survival in a mouse model of surfactant B deficiency
Surfactant protein B (SP-B) deficiency is a genetic lung disease that results in lethal respiratory distress within months of birth. Here, the authors describe a gene therapy strategy using a rationally designed AAV6 capsid that restores surfactant homeostasis, prevents lung injury, and improves survival in a mouse model of SP-B deficiency.
- Martin H. Kang
- , Laura P. van Lieshout
- & Bernard Thébaud
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Article
| Open AccessWithin-host microevolution of Streptococcus pneumoniae is rapid and adaptive during natural colonisation
Streptococcus pneumoniae is an opportunistic pathogen and asymptomatic colonization is a precursor for invasive disease. Here the authors show rapid within-host evolution of naturally acquired pneumococci in ninety-eight infants driven by high nucleotide substitution rates and intra-host homologous recombination.
- Chrispin Chaguza
- , Madikay Senghore
- & Brenda A. Kwambana-Adams
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| Open AccessAnalysis of immune, microbiota and metabolome maturation in infants in a clinical trial of Lactobacillus paracasei CBA L74-fermented formula
Milk breastfeeding and prebiotic-supplemented formulas have varying effects on the infant gut microbiome. Here, in a randomized controlled clinical trial, the authors investigate the effects of a Lactobacillus paracasei-fermented formula on the immune defense mechanisms, microbiota and its metabolome in full term infants.
- Paola Roggero
- , Nadia Liotto
- & Maria Rescigno
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| Open AccessA randomized trial evaluating virus-specific effects of a combination probiotic in children with acute gastroenteritis
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.
- Stephen B. Freedman
- , Jianling Xie
- & Marc H. Gorelick
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| Open AccessMaternal carriage of Prevotella during pregnancy associates with protection against food allergy in the offspring
Incidence of food allergy in westernized populations is associated with low abundance of Prevotella. Here, the authors analyse the microbiome of a mother-infant prebirth cohort and find that maternal carriage, but not infant carriage, of P. copri during pregnancy predicts the absence of food allergy in the offspring.
- Peter J. Vuillermin
- , Martin O’Hely
- & Esther Bandala Sanchez
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| Open AccessMass cytometry reveals cellular fingerprint associated with IgE+ peanut tolerance and allergy in early life
Food allergy is triggered by IgE, but some individuals are not allergic to peanuts despite making peanut-specific IgE, and are considered peanut-tolerant. Here, the authors identify differences in blood immune cell composition of peanut-allergic and tolerant infants using mass cytometry, which may help uncover the mechanism of allergic tolerance.
- Melanie R. Neeland
- , Sandra Andorf
- & Kari C. Nadeau
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| Open AccessTracking regional brain growth up to age 13 in children born term and very preterm
In this longitudinal study, the authors tracked the course of brain development from birth to adolescence (age 13 years) and examined the effects of very preterm birth. Very preterm children showed slower brain growth from age 0 (term equivalent) to age 7.
- Deanne K. Thompson
- , Lillian G. Matthews
- & Peter J. Anderson
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| Open AccessOil-in-water emulsion adjuvants for pediatric influenza vaccines: a systematic review and meta-analysis
Here, the authors meta-analyze clinical trials comparing adjuvanted and non-adjuvanted influenza vaccines in children and find that oil-in-water emulsion adjuvant improves the efficacy of inactivated influenza vaccines in healthy immunologically naive children.
- Yu-Ju Lin
- , Chiao-Ni Wen
- & Chi-Tai Fang
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| Open AccessStress sensitization among severely neglected children and protection by social enrichment
Early adversity may sensitize people to the effects of later stress, amplifying psychopathology risk. Here, the authors show this stress sensitization effect for adolescents who experienced prolonged institutional deprivation in childhood, but not those assigned to foster care intervention.
- Mark Wade
- , Charles H. Zeanah
- & Charles A. Nelson
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| Open AccessThe upper-airway microbiota and loss of asthma control among asthmatic children
How the airway microbiome influences asthma pathophysiology remains unclear. Here, the authors analyse nasal samples of cohort of school-age children with persistent asthma and find that the microbiota’s patterns and composition at time of early loss of asthma control associate with severe asthma exacerbations.
- Yanjiao Zhou
- , Daniel Jackson
- & Avraham Beigelman
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| Open AccessImpact of delivery mode-associated gut microbiota dynamics on health in the first year of life
Here, in a cohort of infants unexposed to maternal antibiotics, the authors analyse the gut microbiome development of children born naturally and by caesarean section, finding a higher abundance of known pathogens in the latter group, and an association between these bacteria and a higher incidence of respiratory infections in the first year of life.
- Marta Reyman
- , Marlies A. van Houten
- & Debby Bogaert
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| Open AccessGenome-wide association study reveals dynamic role of genetic variation in infant and early childhood growth
Changes in body mass index (BMI) during infancy and childhood follow a well-characterized pattern. Here, Helgeland et al. perform genome-wide association studies for BMI at 12 time points between birth and 8 years of age and find transient associations at the LEP and LEPR loci.
- Øyvind Helgeland
- , Marc Vaudel
- & Pål Rasmus Njølstad
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| Open AccessTuberculous meningitis in children is characterized by compartmentalized immune responses and neural excitotoxicity
Tuberculosis meningitis (TBM) is a severe form of TB with limited treatment options. Here, the authors perform RNA sequencing on whole blood and on ventricular and lumbar cerebrospinal fluid (CSF) samples from pediatric patients treated for TBM to characterize the immune response and tissue damage.
- Ursula K. Rohlwink
- , Anthony Figaji
- & Rachel P. J. Lai
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| Open AccessA murine neonatal model of necrotizing enterocolitis caused by anemia and red blood cell transfusions
The development of neonatal necrotising enterocolitis has been temporally associated with red blood cell transfusions in retrospective human studies. Here, the authors develop a neonatal mouse model of necrotising enterocolitis in anaemic mice receiving red blood cell transfusion that recapitulates features of the human condition.
- Krishnan MohanKumar
- , Kopperuncholan Namachivayam
- & Akhil Maheshwari
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| Open AccessMeta-analysis of epigenome-wide association studies in neonates reveals widespread differential DNA methylation associated with birthweight
Birthweight has been found to associate with later-life health outcomes. Here the authors perform a meta-analysis of epigenome-wide association studies of 8,825 neonates from 24 birth cohorts in the Pregnancy And Childhood Epigenetics Consortium, identifying differentially methylated CpGs in neonatal blood that associate with birthweight.
- Leanne K. Küpers
- , Claire Monnereau
- & Janine F. Felix
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| Open AccessPerinatal factors affect the gut microbiota up to four years after birth
Early life microbiome is affected by factors such as mode of delivery, gestational age at birth and feeding regime. Here, the authors show that gestational age at birth still imprints on the microbiome at four years of age, suggesting a link between altered microbiome in prematurity and long term health implications.
- Fiona Fouhy
- , Claire Watkins
- & Catherine Stanton
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| Open AccessThe indirect health effects of malaria estimated from health advantages of the sickle cell trait
Estimates of the burden of malaria often don't take wider, indirect effects on overall health into consideration. Here, Uyoga et al. estimate the indirect impact of malaria on children’s health in a case-control study, using the sickle cell trait as a proxy indicator for an effective intervention.
- Sophie Uyoga
- , Alex W. Macharia
- & Thomas N. Williams
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| Open AccessNeurodevelopmental milestones and associated behaviours are similar among healthy children across diverse geographical locations
It is unclear whether the sequence and timing of early life neurodevelopment varies across human populations, excluding the effects of disease or malnutrition. Here, the authors show that children of healthy, urban, educated mothers show very similar development across five geographically diverse populations.
- José Villar
- , Michelle Fernandes
- & Stephen Kennedy
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| Open AccessA child with perinatal HIV infection and long-term sustained virological control following antiretroviral treatment cessation
Some perinatally HIV infected children who have received early antiretroviral therapy (ART) show long-term sustained virological control after ART cessation. Here the authors describe a case who, at age 9.5 years, shows normal CD4:CD8 T cell ratios and has no detectable levels of replication-competent virus.
- Avy Violari
- , Mark F. Cotton
- & Caroline T. Tiemessen
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| Open AccessMeta-analysis of effects of exclusive breastfeeding on infant gut microbiota across populations
Studies on the effects of breastfeeding on the infant gut microbiota have provided inconsistent results. Here, Ho et al. perform a meta-analysis of seven studies across different populations, supporting that exclusive breastfeeding is associated with short-term and long-term alterations in the infant gut microbiota.
- Nhan T. Ho
- , Fan Li
- & Louise Kuhn
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Article
| Open AccessClonal dynamics in osteosarcoma defined by RGB marking
Osteosarcoma is a heterogeneous bone tumour with a high mutational rate. Here the authors use an RGB-based single-cell tracking system to track clonal dynamics in a mouse model of osteosarcoma, which their findings indicate follows a neutral evolution model in which different clones simultaneously coexist and propagate.
- Stefano Gambera
- , Ander Abarrategi
- & Javier García-Castro
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| Open AccessMetaproteomics reveals associations between microbiome and intestinal extracellular vesicle proteins in pediatric inflammatory bowel disease
Gut microbial dysbiosis has been implicated in the pathogenesis of inflammatory bowel disease. Here, the authors examine host-microbiota protein interactions that occur in inflammatory bowel disease; they show an upregulation in proteins related to antimicrobial activities, and alterations in intestinal extracellular vesicles that are associated with aberrant microbiota-interactions.
- Xu Zhang
- , Shelley A. Deeke
- & Daniel Figeys
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| Open AccessMacrophage-derived IL-1β/NF-κB signaling mediates parenteral nutrition-associated cholestasis
The authors previously developed a mouse model of parenteral nutrition-associated cholestasis (PNAC) that is dependent on parenteral phytosterols and intestinal injury with DSS. Here they refine the model and show that PNAC pathology is dependent on recruitment of hepatic macrophages and IL-1 signaling.
- Karim C. El Kasmi
- , Padade M. Vue
- & Ronald J. Sokol
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| Open AccessDelayed gut microbiota development in high-risk for asthma infants is temporarily modifiable by Lactobacillus supplementation
Gut microbial dysbiosis in infancy is associated with childhood atopy and the development of asthma. Here, the authors show that gut microbiota perturbation is evident in the very earliest stages of postnatal life, continues throughout infancy, and can be partially rescued by Lactobacillus supplementation in high-risk for asthma infants.
- Juliana Durack
- , Nikole E. Kimes
- & Susan V. Lynch
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| Open AccessMaturation of the gut microbiome and risk of asthma in childhood
Colonization of commensal bacteria is thought to impact immune development, especially in the earliest years of life. Here, the authors show, by analyzing the development of the gut microbiome of 690 children, that microbial composition at the age of 1 year is associated with asthma diagnosed in the first 5 years of life.
- Jakob Stokholm
- , Martin J. Blaser
- & Hans Bisgaard
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| Open AccessIntegrative genomics of microglia implicates DLG4 (PSD95) in the white matter development of preterm infants
Inflammation mediated by microglia plays a key role in brain injury associated with preterm birth, but little is known about the microglial response in preterm infants. Here, the authors integrate molecular and imaging data from animal models and preterm infants, and find that microglial expression of DLG4 plays a role.
- Michelle L. Krishnan
- , Juliette Van Steenwinckel
- & Pierre Gressens
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| Open AccessGenome-wide approach identifies a novel gene-maternal pre-pregnancy BMI interaction on preterm birth
Preterm birth (PTB) has high prevalence and PTB infants have greater risk for mortality. Here, Hong and colleagues perform a genome-wide gene × environment interaction analysis and find that maternalCOL24A1variants have a significant interaction with maternal pre-pregnancy obesity in increasing PTB risk.
- Xiumei Hong
- , Ke Hao
- & Xiaobin Wang
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| Open AccessThe child brain computes and utilizes internalized maternal choices
Mothers advocate eating healthy foods while children like to eat tasty foods. Lim and colleagues demonstrate that children incorporate their mothers' food choices while deciding what to eat as well as provide the neural correlates of this decision making process.
- Seung-Lark Lim
- , J. Bradley C. Cherry
- & Amanda S. Bruce
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| Open AccessIntestinal microbiome is related to lifetime antibiotic use in Finnish pre-school children
The impact of antibiotics on the microbiome and health of children is poorly understood. Here, Korpela et al. study the gut microbiome of 142 children and show that the use of macrolides, but not penicillins, is associated with long-lasting shifts in microbiota composition and increased risk of asthma and overweight.
- Katri Korpela
- , Anne Salonen
- & Willem M. de Vos
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| Open AccessTrained immunity in newborn infants of HBV-infected mothers
The ability to fight infections matures after birth and is thus termed ‘trained immunity’. Here the authors show that cord blood cells from hepatitis B virus-infected mothers respond more strongly to bacterial infections, suggesting that viral exposure in uteropromotes trained immunity in newborns.
- Michelle Hong
- , Elena Sandalova
- & Antonio Bertoletti