Niche-derived Semaphorin 4A safeguards functional identity of myeloid-biased hematopoietic stem cells.

Somatic stem cell pools comprise diverse, highly specialized subsets whose individual contribution is critical for the overall regenerative function. In the bone marrow, myeloid-biased hematopoietic stem cells (myHSCs) are indispensable for replenishment of myeloid cells and platelets during inflammatory response but, at the same time, become irreversibly damaged during inflammation and aging. Here we identify an extrinsic factor, semaphorin 4A (Sema4A), which non-cell-autonomously confers myHSC resilience to inflammatory stress.

Anaphylaxis definition, overview, and clinical support tool: 2024 consensus report.

Background: The 2006 National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network (NIAID/FAAN) anaphylaxis criteria are widely used in clinical care and research. In 2020, the World Allergy Organization (WAO) published modified criteria that have not been uniformly adopted. Different criteria contribute to inconsistent care and research outcomes.

Comparison of Chart Review and Administrative Data in Developing Predictive Models for Readmissions in Chronic Obstructive Pulmonary Disease.

This study aimed to evaluate the performance of machine learning models for predicting readmission of patients with Chronic Obstructive Pulmonary Disease (COPD) based on administrative data and chart review data. The study analyzed 4,327 patient encounters from the University of Chicago Medicine to assess the risk of readmission within 90 days after an acute exacerbation of COPD. Two random forest prediction models were compared.

Therapeutic interception in individuals at risk of rheumatoid arthritis to prevent clinically impactful disease.

Multiple clinical trials for rheumatoid arthritis (RA) prevention have been completed. Here, we set out to report on the lessons learnt from these studies. Researchers who conducted RA prevention trials shared the background, rationale, approach and outcomes and evaluated the lessons learnt to inform the next generation of RA prevention trials.

Comparative analysis of ambient, in-home, and personal exposures reveals associations between breathing zone pollutant levels and asthma exacerbations in high-risk children.

Background: Air pollution is associated with poor asthma outcomes in children. However, most studies focus on ambient or indoor monitor pollution levels. Few studies evaluate breathing zone exposures, which may be more consequential for asthma outcomes.

Diversity of complementary diet and early food allergy risk.

Introduction: Diet diversity (DD) in infancy may be protective for early food allergy (FA) but there is limited knowledge about how DD incorporating consumption frequency influences FA risk.

Methods: Three measures of DD were investigated in 2060 infants at 6 and/or at 9 months of age within the NorthPop Birth Cohort Study: a weighted DD score based on intake frequency, the number of introduced foods, and the number of introduced allergenic foods. In multivariable logistic regression models based on directed acyclic graphs, associations to parentally reported physician-diagnosed FA at age 9 and 18 months were estimated, including sensitivity and stratified analyses.

A Comparative Environmental Impact Analysis of Screening Tests for Colorectal Cancer.

Background: Healthcare is a major contributor to global greenhouse gas emissions. Colorectal cancer (CRC) screening is one of the most widely used healthcare services in the US, indicated for approximately 134 million adults. Recommended screening options include fecal immunochemical tests (FITs) every year, CT colonographies (CTCs) every 5 years, or colonoscopies every 10 years.

Oxidative Gaseous Air Pollutant Exposure Interacts with PNPLA3-I148M Genotype to Influence Liver Fat Fraction and Multi-Omics Profiles in Young Adults.

PNPLA3-I148M genotype is the strongest predictive single-nucleotide polymorphism for liver fat. We examine whether PNPLA3-I148M modifies associations between oxidative gaseous air pollutant exposure (O) with i) liver fat and ii) multi-omics profiles of miRNAs and metabolites linked to liver fat. Participants were 69 young adults (17-22 years) from the Meta-AIR cohort.

Longitudinal integrated proteomic and metabolomic skin changes in atopic dermatitis patients treated with dupilumab.

Background: Inhibition of IL-4/IL-13 driven inflammation by dupilumab has shown significant clinical benefits in treatment of atopic dermatitis (AD).

Objective: To assess longitudinal protein and metabolite composition in AD skin during dupilumab treatment.

Methods: Skin tape strip (STS) were collected from lesional/non-lesional skin of 20 AD patients during 16-week dupilumab treatment and from 20 healthy volunteers (HV) followed for 16-weeks.

Physiologic Pulmonary Phenotyping of Infants Born Preterm and Post-Discharge Respiratory Morbidity.

Objectives: To determine whether airway and parenchymal function identifies subgroups of infants born preterm according to the predominant pulmonary pathophysiology, and whether these subgroups have different risks for respiratory disease during infancy.

Study Design: We prospectively enrolled a cohort of 125 infants born preterm with planned clinical follow-up after NICU discharge. The study included monthly questionnaires for wheeze and visits to a physician or care provider for any respiratory illness.

Phospho-flow cytometry assays for diagnostic use - A discussion of assay utility and assay development and validation challenges.

Detection of changes in phosphorylation of cell signaling molecules using flow cytometry is termed "phosphoflow" or "phospho-flow cytometry". Phosphoflow has wide application for basic research into the mechanics of cell signaling, for evaluating aberrant signaling in cancerous cells and tissues, for studying efficacy or off-target effects during drug and vaccine development, and for functional assessment of pathogenic variants of genes that are known to play a role in development or function of the immune system. Phosphoflow has not been widely adopted in clinical laboratories owing to the challenges with developing and validating robust assays consistent with clinical laboratory regulatory standards.

One hundred thirty-four germ line PU.1 variants and the agammaglobulinemic patients carrying them.

Leukopoiesis is lethally arrested in mice lacking the master transcriptional regulator PU.1. Depending on the animal model, subtotal PU.

Development of a drug allergy alert tiering algorithm for penicillins and cephalosporins.

Introduction: Limited research is available regarding recommendations about which drug allergy alerts (DAAs) in clinical decision support (CDS) systems should interrupt provider workflow. The objective was to evaluate the frequency of penicillin and cephalosporin DAA overrides at two institutions. A secondary objective was to redesign DAAs using a new tiered alerting system based on patient factors.

Management of children with food allergies by allergists in the United States.

Background: Management of patients with food allergies is complex, especially in cases of patients with multiple and potentially severe food allergies. Although international guidelines exist for food allergy management, the role of the allergist in the decision-making process is key.

Objective: Our aim was to investigate the management patterns and educational needs of practicing allergists treating patients with food allergies.

Cost-effectiveness of watchful waiting versus immediate emergency department transfer after epinephrine autoinjector use in Canada.

Background: Until recently, immediate emergency department (ED) transfer after food-related anaphylactic reactions was recommended regardless of symptom resolution following use of an epinephrine autoinjector (EAI). We evaluated the cost-effectiveness of delayed ED transfer after EAI use in non-medical settings (watchful waiting) compared to immediate ED transfer among pediatric patients with food allergies in Canada.

Methods: We developed a probabilistic Markov model of individuals starting at age of one year who are at risk of severe food-related allergic reactions requiring epinephrine.

Healthy Aging and the Gut Microbiome in People With and Without HIV.

Background: Aging-related comorbidities are more common in people with human immunodeficiency virus (HIV) compared to people without HIV. The gut microbiome may play a role in healthy aging; however, this relationship remains unexplored in the context of HIV.

Methods: 16S rRNA gene sequencing was conducted on stool from 1409 women (69% with HIV; 2304 samples) and 990 men (54% with HIV; 1008 samples) in the MACS/WIHS Combined Cohort Study.

Secondhand vape exposure regulation of CFTR and immune function in cystic fibrosis.

Secondhand smoke exposure (SHSe) is a public health threat for people with cystic fibrosis (CF) and other lung diseases. Primary smoking reduces CFTR channel function, the causative defect in CF. We reported that SHSe worsens respiratory and nutritional outcomes in CF by disrupting immune responses and metabolic signaling.

C-Reactive Protein Changes in Adult and Pediatric People With Cystic Fibrosis During Treatment of Pulmonary Exacerbations.

Objective: Although studies have examined changes in C-reactive protein (CRP) during pulmonary exacerbations (PEX) in people with cystic fibrosis (PwCF), few have evaluated CRP profiles across age groups. Here, we characterize age-related CRP responses to PEX treatment.

Methods: We measured CRP concentrations at the beginning and end of intravenous (IV) antibiotic therapy for PEX in 100 pediatric and 147 adult PwCF at 10 US CF Centers.

Using Community Engagement to Create a Telecoaching Intervention to Improve Self-Management in Adolescents and Young Adults With Cystic Fibrosis: Qualitative Study.

Background: Adolescents and young adults (AYA) with cystic fibrosis (CF) are at risk for deviating from their daily treatment regimen due to significant time burden, complicated daily therapies, and life stressors. Developing patient-centric, effective, engaging, and practical behavioral interventions is vital to help sustain therapeutically meaningful self-management.

Objective: This study aimed to devise and refine a patient-centered telecoaching intervention to foster self-management in AYA with CF using a combination of intervention development approaches, including an evidence- and theory-based approach (ie, applying existing theories and research evidence for behavior change) and a target population-centered approach (ie, intervention refinement based on the perspectives and actions of those individuals who will use it).

Integrated Phase I Pharmacokinetics and Pharmacodynamics of Epinephrine Administered via Sublingual Film, Autoinjector, or Manual Injection.

Background: Epinephrine is the first-line treatment for anaphylaxis and is administered via intramuscular (IM) or subcutaneous (SC) injection. AQST-109, a sublingual film containing a prodrug of epinephrine, is in development as an alternative delivery method for the treatment of severe allergic reactions including anaphylaxis.

Objective: To compare the pharmacokinetics (PK) and pharmacodynamics (PD) of epinephrine following administration of AQST-109 to epinephrine delivered by manual IM injection and epinephrine autoinjectors (EAIs).

Digital Health for Asthma Management: Electronic Medication Monitoring for Adherence as a Case Example.

Digital health is an umbrella term for components of healthcare utilizing computer platforms, software, connectivity and sensors to augment the recording, documentation and communication of clinical information. The functions of digital health may be viewed in three domains: 1) the repository for patient information, 2) monitoring devices and 3) communication tools. Monitoring devices have provided robust information as diagnostic and prognostic tools in office and hospital settings.

Safety, Tolerability, and Pharmacokinetics of Long-Acting Broadly Neutralizing HIV-1 Monoclonal Antibody VRC07523LS in Newborn Infants Exposed to HIV-1.

Background: Vertical HIV-1 transmission despite antiretroviral therapy may be mitigated by use of long-acting, broadly neutralizing, monoclonal antibodies (bNAb) such as VRC07523LS. The present study was designed to determine the safety and pharmacokinetics of VRC07523LS.

Methods: VRC07523LS, 80 mg/dose, was administered subcutaneously after birth to non-breastfed (Cohort 1; N=11, enrolled in USA) and breastfed (Cohort 2; N=11, enrolled in South Africa and Zimbabwe) infants exposed to HIV-1.

Pharmacokinetics and safety of bictegravir in pregnant and postpartum persons with HIV and their infants.

Background: Limited data exist on bictegravir pharmacokinetics in pregnancy among persons with HIV (PWH) and infant washout.

Setting: Nonrandomized, open-label, multi-center phase-IV prospective study of bictegravir pharmacokinetics and safety in pregnant PWH and their infants.

Methods: Steady-state 24-hour pharmacokinetic sampling of oral bictegravir 50 mg once daily (a component of fixed-dose combination bictegravir/emtricitabine/tenofovir alafenamide) during the 2nd and 3rd trimesters and postpartum was performed.

The impact of highly effective modulator therapy on sinusitis and dysosmia in young children with cystic fibrosis: a prospective study protocol.

Background: Chronic rhinosinusitis (CRS) and olfactory dysfunction (OD) are prevalent disease complications in people with cystic fibrosis. These understudied comorbidities significantly impact quality of life. The impact of highly effective modulator therapy (HEMT) in young children with cystic fibrosis (YCwCF) on these disease complications is unknown.

Blood absolute lymphocyte count and trajectory are important in understanding severe COVID-19.

Background: Low blood absolute lymphocyte count (ALC) may predict severe COVID-19 outcomes. Knowledge gaps remain regarding the relationship of ALC trajectory with clinical outcomes and factors associated with lymphopenia.

Methods: Our post hoc analysis of the Therapeutics for Inpatients with COVID-19 platform trial utilized proportional hazards models to assess relationships between Day (D) 0 lymphopenia (ALC < 0.