Germline susceptibility from broad genomic profiling of pediatric brain cancers.

Background: Identifying germline predisposition in CNS malignancies is of increasing clinical importance, as it contributes to diagnosis and prognosis, and determines aspects of treatment. The inclusion of germline testing has historically been limited due to challenges surrounding access to genetic counseling, complexity in acquiring a germline comparator specimen, concerns about the impact of findings, or cost considerations. These limitations were further defined by the breadth and scope of clinical testing to precisely identify complex variants as well as concerns regarding the clinical interpretation of variants including those of uncertain significance.

Combinatorial macrophage induced innate immunotherapy against Ewing sarcoma: Turning "Two Keys" simultaneously.

Background: Macrophages play important roles in phagocytosing tumor cells. However, tumors escape macrophage phagocytosis in part through the expression of anti-phagocytic signals, most commonly CD47. In Ewing sarcoma (ES), we found that tumor cells utilize dual mechanisms to evade macrophage clearance by simultaneously over-expressing CD47 and down-regulating cell surface calreticulin (csCRT), the pro-phagocytic signal.

Exploring the secrets of virus entry: the first respiratory syncytial virus carrying beta lactamase.

Background: Respiratory Syncytial Virus (RSV) presents a significant health threat, especially to young children. In-depth understanding of RSV entry mechanisms is essential for effective antiviral development. This study introduces an innovative RSV variant, featuring the fusion of the beta-lactamase (BlaM) enzyme with the RSV-P phosphoprotein, providing a versatile tool for dissecting viral entry dynamics.

CX3CR1 Is a Receptor for Human Respiratory Syncytial Virus in Cotton Rats.

Respiratory syncytial virus (RSV) has been reported to use CX3CR1 as a receptor on cultured primary human airway epithelial cultures. To evaluate CX3CR1 as the receptor for RSV , we used the cotton rat animal model because of its high permissiveness for RSV infection. Sequencing the cotton rat CX3CR1 gene revealed 91% amino acid similarity to human CX3CR1.

Five Residues in the Apical Loop of the Respiratory Syncytial Virus Fusion Protein F Subunit Are Critical for Its Fusion Activity.

The respiratory syncytial virus (RSV) fusion (F) protein is a trimeric, membrane-anchored glycoprotein capable of mediating both virus-target cell membrane fusion to initiate infection and cell-cell fusion, even in the absence of the attachment glycoprotein. The F protein is initially expressed in a precursor form, whose functional capabilities are activated by proteolysis at two sites between the F and F subunits. This cleavage results in expression of the metastable and high-energy prefusion conformation.

Molecular mechanism of respiratory syncytial virus fusion inhibitors.

Respiratory syncytial virus (RSV) is a leading cause of pneumonia and bronchiolitis in young children and the elderly. Therapeutic small molecules have been developed that bind the RSV F glycoprotein and inhibit membrane fusion, yet their binding sites and molecular mechanisms of action remain largely unknown. Here we show that these inhibitors bind to a three-fold-symmetric pocket within the central cavity of the metastable prefusion conformation of RSV F.

Targeting RSV with vaccines and small molecule drugs.

Respiratory syncytial virus (RSV) is the most significant cause of pediatric respiratory infections. Palivizumab (Synagis®), a humanized monoclonal antibody, has been used successfully for a number of years to prevent severe RSV disease in at-risk infants. However, despite intense efforts, there is no approved vaccine or small molecule drug for RSV.

A comparison of analgesic management for emergency department patients with sickle cell disease and renal colic.

Objectives: To determine whether there is a difference in time to initial analgesic for patients with acute pain from sickle cell disease (SCD) versus renal colic (RC) and to identify factors contributing to variance in time to analgesic.

Methods: A retrospective cohort study of the adult emergency department (ED) patients with acute pain from SCD and RC in an urban ED (final ED discharge ICD-9 diagnosis codes were included). A structured medical record review abstracted the demographics, arrival shift, triage level, initial pain score, triage time, and time of initial analgesic dose.