The vertebrate segmentation clock drives segmentation by stabilizing Dusp phosphatases in zebrafish.

Pulsatile activity of the extracellular signal-regulated kinase (ERK) controls several cellular, developmental, and regenerative programs. Sequential segmentation of somites along the vertebrate body axis, a key developmental program, is also controlled by ERK activity oscillation. The oscillatory expression of Her/Hes family transcription factors constitutes the segmentation clock, setting the period of segmentation.

Pediatric firearm injuries and socioeconomic vulnerability before and during the COVID-19 pandemic.

Background: Pediatric firearm injuries disproportionately affect groups experiencing socioeconomic disadvantage. Firearm injuries increased during the COVID-19 pandemic, but the impact on communities by degree of socioeconomic disadvantage is unknown. We examined the association between socioeconomic vulnerability and change in pediatric firearm injuries before versus during the pandemic.

Genotype-immunophenotype relationships in -mutant AML clonal evolution uncovered by single cell multiomic analysis.

Acute myeloid leukemia (AML) is a multi-clonal disease, existing as a milieu of clones with unique but related genotypes as initiating clones acquire subsequent mutations. However, bulk sequencing cannot fully capture AML clonal architecture or the clonal evolution that occurs as patients undergo therapy. To interrogate clonal evolution, we performed simultaneous single cell molecular profiling and immunophenotyping on 43 samples from 32 -mutant AML patients at different stages of disease.

SOX17-Associated Pulmonary Hypertension in Children: A Distinct Developmental and Clinical Syndrome.

Objective: To characterize clinical, hemodynamic, imaging, and pathologic findings in children with pulmonary arterial hypertension (PAH) and variants in SRY-box transcription factor 17 (SOX17), a novel risk gene linked to heritable and congenital heart disease-associated PAH.

Study Design: We assembled a multi-institutional cohort of children with PAH and SOX17 variants enrolled in the Pediatric Pulmonary Hypertension Network (PPHNet) and other registries. Subjects were identified through exome and PAH gene panel sequencing.

Hypoglycemia in Pregnant Women with Type 1 Diabetes: Is It Inevitable?

The human body has abundant mechanisms to counteract hypoglycemia and prevent neuroglycopenia primarily involving the secretion of glucagon and adrenalin. Within several years from the onset of diabetes, people with type 1 diabetes lose their ability to mount a counterregulatory response to hypoglycemia and develop hypoglycemia unawareness, thus being at risk for deteriorating to a state of severe hypoglycemia and neuroglycopenia. Pregnant individuals with type 1 diabetes are particularly prone to experience severe hypoglycemia during the first half of pregnancy.

Serum Dioxin Levels in a Subset of Participants of the East Palestine, Ohio Train Derailment Health Tracking Study.

A February 3, 2023 train derailment and subsequent burn released hazardous chemicals into East Palestine, Ohio. One potential exposure was polychlorinated dibenzo-p-dioxins, dibenzofurans, and coplanar polychlorinated biphenyls (cPCBs), collectively referred to as dioxins. Many studies have linked dioxins to numerous health effects.

Supporting the Well-Being of Children and Youth With Special Health Care Needs: NASEM Proceedings.

Children and youth with special health care needs (CYSHCN) are living longer than ever. These advances come with a price: Patients, families, communities, and systems must absorb the challenges of chronic caregiving, including protracted stress and poor mental health. In 2023, the National Academies of Science, Engineering, and Medicine convened thought-leaders for conversations about supporting the emotional well-being of CYSHCN and their families.

Association of Liver Damage and Quasispecies Maturity in Chronic HCV Patients: The Fate of a Quasispecies.

Viral diversity and disease progression in chronic infections, and particularly how quasispecies structure affects antiviral treatment, remain key unresolved issues. Previous studies show that advanced liver fibrosis in long-term viral infections is linked to higher rates of antiviral treatment failures. Additionally, treatment failure is associated with high quasispecies fitness, which indicates greater viral diversity and adaptability.

Humanin-G Ameliorates Hemorrhage-Induced Acute Lung Injury in Mice Through AMPKα1-Dependent and -Independent Mechanisms.

: The severity of acute lung injury is significantly impacted by age and sex in patients with hemorrhagic shock. AMP-activated protein kinase (AMPK) is a crucial regulator of energy metabolism but its activity declines with aging. Humanin is a mitochondrial peptide that exerts cytoprotective effects in response to oxidative stressors and is associated with longevity.

D389V Variant Induces Hypercontractility in Cardiac Organoids.

, encoding cardiac myosin binding protein-C (cMyBP-C), is the most mutated gene known to cause hypertrophic cardiomyopathy (HCM). However, since little is known about the underlying etiology, additional in vitro studies are crucial to defining the underlying molecular mechanisms. Accordingly, this study aimed to investigate the molecular mechanisms underlying the pathogenesis of HCM associated with a polymorphic variant (D389V) in by using isogenic human-induced pluripotent stem cell (hiPSC)-derived cardiac organoids (hCOs).

Gucy1α1 specifically marks kidney, heart, lung and liver fibroblasts.

Fibrosis is a common outcome of numerous pathologies, including chronic kidney disease (CKD), a progressive renal function deterioration. Current approaches to target activated fibroblasts, key effector contributors to fibrotic tissue remodeling, lack specificity. Here, we report Gucy1α1 as a specific kidney fibroblast marker.

Elexacaftor/tezacaftor/ivacaftor and mental health: A workshop report from the Cystic Fibrosis Foundation's Prioritizing Research in Mental Health working group.

Background: This report summarizes the 2023 inaugural annual meeting of the Cystic Fibrosis Foundation's Prioritizing Research in Mental Health (PRIME) working group. This workshop focused on mental health and elexacaftor/tezacaftor/ivacaftor (ETI).

Methods: We reviewed existing literature and identified key gaps and study design considerations in preclinical work, pharmacokinetics/pharmacodynamics, mood/anxiety, quality of life/self-perception, neuropsychological symptoms, sleep, and symptom management.

Prostate ablation for the management of localized prostate cancer.

Purpose: To evaluate the oncological and genitourinary outcomes of various forms of prostate ablation for localized prostate cancer.

Methods: A prospectively managed database included men with localized prostate cancer who underwent prostate ablation during January 2018-August 2023. Patients received either whole or partial-gland ablation using 1 of 3 energy modalities: cryotherapy, High Intensity Focused Ultrasound (HIFU), or Irreversible electroporation (IRE).

The Homeobox Transcription Factor Cux1 Coordinates Postnatal Epithelial Developmental Timing but Is Dispensable for Lung Organogenesis and Regeneration.

Lung epithelial progenitors use a complex network of known and predicted transcriptional regulators to influence early lung development. Here, we evaluate the function of one predicted regulator, Cux1, that we identified from transcriptional regulatory analysis of the SOX9+ distal lung progenitor network. We generated a new Cux1-floxed mouse model and created an epithelial-specific knockout of Cux1 using Shh-Cre (Cux1).

Use of glucagon-like polypeptide 2 analogs for intestinal failure.

Introduction: Over a half century ago, a component of glucagon was found to have potent gastrointestinal effects. Shortly after proglucagon was sequenced, its component peptides were characterized, and glucagon-like polypeptide-2 (GLP-2) was noted to have the most potent intestinotrophic properties improving fluid and electrolyte balance in experimental animals and humans.

Areas Covered: Glucagon-like polypeptide-1 (GLP-1) slows small intestinal motility more effectively, but its intestinotrophic properties are weaker.

Candidate Tear-Based Uveitis Biomarkers in Children with JIA Based on Arthritis Activity and Topical Corticosteroid Use.

Background: Uveitis is an inflammatory ocular disease secondary to disruption of the retinal pigmented epithelium (RPE) and blood retinal barrier (BRB). Known clinical factors do not accurately predict uveitis risk in Juvenile Idiopathic Arthritis (JIA). Tear fluid is easily obtained for biomarker study.

Tandem mass spectrometry of serum cholestanoic (C) acids - Typical concentration ranges and application to the study of peroxisomal biogenesis disorders.

Background: Primary bile acid synthesis is impaired in peroxisomal disorders, leading to the accumulation of long-chain bile acids, specifically dihydroxycholestanoic and trihydroxycholestanoic acids. Quantification of the diastereoisomers of these C bile acids is essential for the differential diagnosis of these disorders.

Methods: High-performance liquid chromatography electrospray ionization-tandem mass spectrometry with stable-isotope dilution was used to quantify all eight diastereoisomers of cholestanoic acids in serum.

Dihydroxyacetone phosphate is a novel predictor of hepatic fibrosis in Latino adolescents with obesity.

Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common pediatric liver disease and can progress to liver fibrosis. Latino adolescents have increased MASLD and fibrosis risk. While fibrosis is diagnosed by biopsy or imaging, more accessible, noninvasive, and economical screening methods are needed.