The WOCA negative pressure wound therapy device designed for low resource settings.

Negative Pressure Wound Therapy (NPWT) is a treatment that promotes healing of chronic wounds. Despite high prevalence of chronic wounds in Low- and Middle-Income Countries (LMICs), NPWT devices are not available nor affordable. This study aims to improve chronic wound care in LMICs by presenting the Wound Care (WOCA) system, designed for building, testing and use in LMICs.

Estimated Vaccine Effectiveness for Pediatric Patients With Severe Influenza, 2015-2020.

Importance: Increasing the understanding of vaccine effectiveness (VE) against levels of severe influenza in children could help increase uptake of influenza vaccination and strengthen vaccine policies globally.

Objective: To investigate VE in children by severity of influenza illness.

Design, Setting, And Participants: This case-control study with a test-negative design used data from 8 participating medical centers located in geographically different US states in the New Vaccine Surveillance Network from November 6, 2015, through April 8, 2020.

Light-Activatable Ubiquitin for Studying Linkage-Specific Ubiquitin Chain Formation Kinetics.

Ubiquitination is a dynamic post-translational modification governing protein abundance, function, and localization in eukaryotes. The Ubiquitin protein is conjugated to lysine residues of target proteins, but can also repeatedly be ubiquitinated itself, giving rise to a complex code of ubiquitin chains with different linkage types. To enable studying the cellular dynamics of linkage-specific ubiquitination, light-activatable polyubiquitin chain formation is reported here.

Antiviral Use Among Children Hospitalized With Laboratory-Confirmed Influenza Illness: A Prospective, Multicenter Surveillance Study.

Background: Guidelines state that all hospitalized children with suspected or confirmed influenza receive prompt treatment with influenza-specific antivirals. We sought to determine the frequency of, and factors associated with, antiviral receipt among hospitalized children.

Methods: We conducted active surveillance of children presenting with fever or respiratory symptoms from 1 December 2016 to 31 March 2020 at 7 pediatric medical centers in the New Vaccine Surveillance Network.

Embracing Professionalism to Cultivate Vaccine Positivity and Reduce Vaccine Hesitancy.

Fueled by the coronavirus disease 2019 pandemic, vaccine hesitancy has become more pronounced and challenging given the increased distrust of science, pervasiveness of misinformation, and polarization of ideas. As such, pediatric providers are increasingly on the frontline of vaccine conversations with their patients, families, colleagues, and communities. To respond effectively to vaccine hesitancy, providers should employ professionalism in all aspects of their practice, including commitment to learning and growth, cultural awareness and humility, ethical responsibility to self and others, oral communication, reliability and dependability, teamwork, critical thinking and quantitative reasoning, and the engagement in public discourse around vaccines.

Respiratory Syncytial Virus Disease Burden and Nirsevimab Effectiveness in Young Children From 2023-2024.

Importance: During the 2023-2024 respiratory syncytial virus (RSV) season in the United States, 2 new RSV prevention products were recommended to protect infants in their first RSV season: nirsevimab and Pfizer's maternal RSV vaccine. Postlicensure studies are needed to assess prevention product impact and effectiveness.

Objective: To compare the epidemiology and disease burden of medically attended RSV-associated acute respiratory illness (ARI) among children younger than 5 years during the 2023-2024 RSV season with 3 prepandemic RSV seasons (2017-2020), estimate nirsevimab effectiveness against medically attended RSV-associated ARI, and compare nirsevimab binding site mutations among circulating RSV in infants with and without nirsevimab receipt.

Underutilization of Influenza Antiviral Treatment Among Children and Adolescents at Higher Risk for Influenza-Associated Complications - United States, 2023-2024.

Annually, tens of thousands of U.S. children and adolescents are hospitalized with seasonal influenza virus infection.

On-time childhood vaccination before and during the COVID-19 pandemic in seven communities: Findings from the New Vaccine Surveillance Network.

Background: The COVID-19 pandemic raised unprecedented challenges to vaccinating children. This multi-center study aimed to compare on-time vaccination of children before and during the COVID-19 pandemic and identify key factors associated with on-time vaccination.

Methods: This study was conducted among children aged 0-6 years enrolled in the New Vaccine Surveillance Network at seven geographically diverse U.

Pediatric Clinical Influenza Disease by Type and Subtype 2015-2020: A Multicenter, Prospective Study.

Background: Previous investigations into clinical signs and symptoms associated with influenza types and subtypes have not definitively established differences in the clinical presentation or severity of influenza disease.

Methods: The study population included children 0 through 17 years old enrolled at 8 New Vaccine Surveillance Network sites between 2015 and 2020 who tested positive for influenza virus by molecular testing. Demographic and clinical data were collected for study participants via parent/guardian interview and medical chart review.

Prevalence of SARS-CoV-2 in Children Identified by Preprocedural Testing at 5 US Children's Hospital Systems.

Background: The burden of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in asymptomatic children was initially presumed to be high, which influenced hospital, school and childcare policies. Before vaccines were widely available, some hospitals implemented universal preprocedural SARS-CoV-2 polymerase chain reaction testing on asymptomatic patients. Understanding SARS-CoV-2 prevalence in asymptomatic children is needed to illuminate the diversity of viral characteristics and inform policies implemented during future pandemics.

Evaluation of a Modified Vesikari Severity Score as a Research Tool for Assessing Pediatric Acute Gastroenteritis.

A modified Vesikari severity score (MVSS) is a useful research tool for assessing severity of acute gastroenteritis. We present a MVSS for studies in which a follow-up assessment of symptoms cannot be obtained. The MVSS significantly correlated with other markers of severity, including illness duration and work and school absenteeism.

Alternating binding and p97-mediated dissociation of SDS22 and I3 recycles active PP1 between holophosphatases.

Protein phosphatase-1 catalytic subunit (PP1) joins diverse targeting subunits to form holophosphatases that regulate many cellular processes. Newly synthesized PP1 is known to be transiently sequestered in an inhibitory complex with Suppressor-of-Dis2-number-2 (SDS22) and Inhibitor-3 (I3), which is disassembled by the ATPases Associated with diverse cellular Activities plus (AAA+) protein p97. Here, we show that the SDS22-PP1-I3 complex also acts as a thermodynamic sink for mature PP1 and that cycles of SDS22-PP1-I3 formation and p97-driven disassembly regulate PP1 function and subunit exchange beyond PP1 biogenesis.

Influenza C virus in U.S. children with acute respiratory infection 2016-2019.

Influenza C virus (ICV) is an orthomyxovirus related to influenza A and B, yet due to few commercial assays, epidemiologic studies may underestimate incidence of ICV infection and disease. We describe the epidemiology and characteristics of ICV within the New Vaccine Surveillance Network (NVSN), a Centers for Disease Control and Prevention (CDC)-led network that conducts population-based surveillance for pediatric acute respiratory illness (ARI). Nasal or/combined throat swabs were collected from emergency department (ED) or inpatient ARI cases, or healthy controls, between 12/05/2016-10/31/2019 and tested by molecular assays for ICV and other respiratory viruses.

COVID-19 Vaccine Hesitancy in Caregivers of Hospitalized Children From 2020 Through 2023.

Objectives: Data on US caregiver perceptions on coronavirus disease 2019 (COVID-19) and COVID-19 vaccination are limited. We identified trends in and associations with COVID-19 vaccine hesitancy in caregivers of hospitalized children.

Methods: Cross-sectional surveys on pediatric COVID-19 disease and vaccine attitudes, behaviors, and beliefs were administered across study years (December 8, 2020-April 5, 2021, November 30, 2021-March 15, 2022, and October 26, 2022-March 15, 2023).

A modular DNA origami nanocompartment for engineering a cell-free, protein unfolding and degradation pathway.

Within the cell, chemical reactions are often confined and organized through a modular architecture. This facilitates the targeted localization of molecular species and their efficient translocation to subsequent sites. Here we present a cell-free nanoscale model that exploits compartmentalization strategies to carry out regulated protein unfolding and degradation.

Respiratory Syncytial Virus-Associated Hospitalizations in Children <5 Years: 2016-2022.

Background: The coronavirus disease 2019 pandemic disrupted respiratory syncytial virus (RSV) seasonality resulting in early, atypical RSV seasons in 2021 and 2022, with an intense 2022 peak overwhelming many pediatric healthcare facilities.

Methods: We conducted prospective surveillance for acute respiratory illness during 2016-2022 at 7 pediatric hospitals. We interviewed parents, reviewed medical records, and tested respiratory specimens for RSV and other respiratory viruses.

Accuracy of Influenza ICD-10 Diagnosis Codes in Identifying Influenza Illness in Children.

Importance: Studies of influenza in children commonly rely on coded diagnoses, yet the ability of International Classification of Diseases, Ninth Revision codes to identify influenza in the emergency department (ED) and hospital is highly variable. The accuracy of newer International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes to identify influenza in children is unknown.

Objective: To determine the accuracy of ICD-10 influenza discharge diagnosis codes in the pediatric ED and inpatient settings.

Durability of Original Monovalent mRNA Vaccine Effectiveness Against COVID-19 Omicron-Associated Hospitalization in Children and Adolescents - United States, 2021-2023.

Pediatric COVID-19 vaccination is effective in preventing COVID-19-related hospitalization, but duration of protection of the original monovalent vaccine during SARS-CoV-2 Omicron predominance merits evaluation, particularly given low coverage with updated COVID-19 vaccines. During December 19, 2021-October 29, 2023, the Overcoming COVID-19 Network evaluated vaccine effectiveness (VE) of ≥2 original monovalent COVID-19 mRNA vaccine doses against COVID-19-related hospitalization and critical illness among U.S.

Enhancing NSCLC recurrence prediction with PET/CT habitat imaging, ctDNA, and integrative radiogenomics-blood insights.

While we recognize the prognostic importance of clinicopathological measures and circulating tumor DNA (ctDNA), the independent contribution of quantitative image markers to prognosis in non-small cell lung cancer (NSCLC) remains underexplored. In our multi-institutional study of 394 NSCLC patients, we utilize pre-treatment computed tomography (CT) and F-fluorodeoxyglucose positron emission tomography (FDG-PET) to establish a habitat imaging framework for assessing regional heterogeneity within individual tumors. This framework identifies three PET/CT subtypes, which maintain prognostic value after adjusting for clinicopathologic risk factors including tumor volume.

Medical Costs of Respiratory Syncytial Virus-Associated Hospitalizations and Emergency Department Visits in Children Aged Younger Than 5 Years: Observational Findings from the New Vaccine Surveillance Network, 2016-2019.

Objective: To assess medical costs of hospitalizations and emergency department (ED) care associated with respiratory syncytial virus (RSV) disease in children enrolled in the New Vaccine Surveillance Network.

Study Design: We used accounting and prospective surveillance data from 6 pediatric health systems to assess direct medical costs from laboratory-confirmed RSV-associated hospitalizations (n = 2007) and ED visits (n = 1267) from 2016 through 2019 among children aged <5 years. We grouped costs into categories relevant to clinical care and administrative billing practices.

VCF1 is a p97/VCP cofactor promoting recognition of ubiquitylated p97-UFD1-NPL4 substrates.

The hexameric AAA+ ATPase p97/VCP functions as an essential mediator of ubiquitin-dependent cellular processes, extracting ubiquitylated proteins from macromolecular complexes or membranes by catalyzing their unfolding. p97 is directed to ubiquitylated client proteins via multiple cofactors, most of which interact with the p97 N-domain. Here, we discover that FAM104A, a protein of unknown function also named VCF1 (VCP/p97 nuclear Cofactor Family member 1), acts as a p97 cofactor in human cells.

Lysosomal damage sensing and lysophagy initiation by SPG20-ITCH.

Cells respond to lysosomal membrane permeabilization by membrane repair or selective macroautophagy of damaged lysosomes, termed lysophagy, but it is not fully understood how this decision is made. Here, we uncover a pathway in human cells that detects lipid bilayer perturbations in the limiting membrane of compromised lysosomes, which fail to be repaired, and then initiates ubiquitin-triggered lysophagy. We find that SPG20 binds the repair factor IST1 on damaged lysosomes and, importantly, integrates that with the detection of damage-associated lipid-packing defects of the lysosomal membrane.