Genome Instability and Senescence Are Markers of Cornelia de Lange Syndrome Cells.

Cornelia de Lange syndrome (CdLS) is a rare, dominantly inherited multisystem developmental disorder. Pathogenic variants in genes encoding the structural subunits and regulatory proteins of the cohesin complex (, , , , and ) are the primary contributors to the pathogenesis of CdLS. Pathogenic variations in these genes disrupt normal cohesin function, leading to the syndrome's diverse and complex clinical presentation.

Chest and spinal disease in patients with progressive neuromuscular disease.

The chest and spine deformity in neuromuscular disease (NMDz) can impact respiratory mechanics and pulmonary function by changing the orientation of the muscles and joints of the respiratory system and placing them in a mechanically unfavorable position. This increases mechanical load on weak respiratory muscles and eventually can cause respiratory failure. Therefore, chest and spine deformity in NMDz will both lead to increased respiratory "load" and decreased respiratory muscle "pump", an exceptionally bad combination.

Extrauterine support of pre-term lambs achieves similar transcriptomic profiling to late pre-term lamb brains.

Our group has developed an extra-uterine environment for newborn development (EXTEND) using an ovine model, that aims to mimic the womb to improve short and long-term health outcomes associated with prematurity. This study's objective was to determine the histologic and transcriptomic consequences of EXTEND on the brain. Histology and RNA-sequencing was conducted on brain tissue from three cohorts of lambs: control pre-term (106-107 days), control late pre-term (127 days), and EXTEND lambs who were born pre-term and supported on EXTEND until late pre-term age (125-128 days).

Integrating parent voices into research at the extremes of prematurity: what are we doing and where should we go?

When a baby is born premature, a landscape of potential problems replaces an imagined future. Outcomes become the measures of success. Researchers are recognizing that we need the direct input of parents to select meaningful outcomes.

Lessons learned from 20 years of preclinical testing in pediatric cancers.

Programs for preclinical testing of targeted cancer agents in murine models of childhood cancers have been supported by the National Cancer Institute (NCI) since 2004. These programs were established to work collaboratively with industry partners to address the paucity of targeted agents for pediatric cancers compared with the large number of agents developed and approved for malignancies primarily affecting adults. The distinctive biology of pediatric cancers and the relatively small numbers of pediatric cancer patients are major challenges for pediatric oncology drug development.

Pediatric subspecialty workforce: what is needed to secure its vitality and survival?

The pediatric subspecialty workforce is challenged by shortages and geographic maldistribution of subspecialists. We invited leaders in pediatrics to discuss how the field's vitality and survival can be secured. These leaders presented their own opinions and not the opinion of the society or organization that they are presenting.

Benefits of Dual Appointments in Academic Research and Bedside Nursing.

Research and clinical practice can inform and improve each other.

Transorbital intraoperative electrocorticography-guided surgical resection for medically refractory developmental epileptic encephalopathy with spike-wave activation in sleep.

Developmental epileptic encephalopathy with spike-wave activation in sleep (DEE-SWAS) is an epilepsy syndrome of childhood characterized by developmental delay or regression with significant abnormal epileptiform activity during sleep. In some cases, DEE-SWAS with an identified focal lesion is treated with surgical resection. The authors report an unusual case of focal DEE-SWAS that was successfully treated via transorbital resection with intraoperative electrocorticography (iECoG).

Nature and Magnitude of Industry Payments to Fellowship Program Directors in Orthopaedic Surgery.

Introduction: Previous research has highlighted conflicts of interest stemming from industry funding and education of orthopaedic surgeons. This study sought to define the nature and magnitude of industry payments to orthopaedic surgery fellowship program directors (FPDs) in the United States.

Methods: This was a retrospective cohort study of orthopaedic surgery FPDs during 2021.

Greater urinary calcium excretion is associated with diminished bone accrual in youth with type 1 diabetes.

Context: The adverse skeletal effects of type 1 diabetes (T1D) include deficient bone accrual and lifelong increased fracture risk. The contributors to impaired bone accrual in people with T1D are incompletely understood.

Objective: To determine if urinary calcium excretion is associated with impaired bone accrual in youth with T1D and to characterize the contribution of glycemic control and markers of bone mineral metabolism to urinary calcium excretion.

Investigation of cryptic JAG1 splice variants as a cause of Alagille syndrome and performance evaluation of splice predictor tools.

Haploinsufficiency of JAG1 is the primary cause of Alagille syndrome (ALGS), a rare, multisystem disorder. The identification of JAG1 intronic variants outside of the canonical splice region as well as missense variants, both of which lead to uncertain associations with disease, confuses diagnostics. Strategies to determine whether these variants affect splicing include the study of patient RNA or minigene constructs, which are not always available or can be laborious to design, as well as the utilization of computational splice prediction tools.

Evolution of Proton Radiation Therapy Brainstem Constraints on the Pediatric Proton/Photon Consortium Registry.

Purpose: Increasing concern that brainstem toxicity incidence after proton radiation therapy might be higher than with photons led to a 2014 University of Florida (UF) landmark paper identifying its risk factors and proposing more conservative dose constraints. We evaluated how practice patterns changed among the Pediatric Proton/Photon Consortium Registry (PPCR).

Material And Methods: This prospective multicenter cohort study gathered data from patients under the age of 22 years enrolled on the PPCR, treated between 2002 and 2019 for primary posterior fossa brain tumors.

Functional characterization of 2,832 JAG1 variants supports reclassification for Alagille syndrome and improves guidance for clinical variant interpretation.

Pathogenic variants in the JAG1 gene are a primary cause of the multi-system disorder Alagille syndrome. Although variant detection rates are high for this disease, there is uncertainty associated with the classification of missense variants that leads to reduced diagnostic yield. Consequently, up to 85% of reported JAG1 missense variants have uncertain or conflicting classifications.