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View article: Multiplex Imaging Mass Cytometry Reveals Prognostic Immunosuppressive Subpopulations and Macrophage-Driven Metastasis in Osteosarcoma
Multiplex Imaging Mass Cytometry Reveals Prognostic Immunosuppressive Subpopulations and Macrophage-Driven Metastasis in Osteosarcoma Open
Background: Metastasis continues to be a leading cause of mortality in osteosarcoma (OS) among pediatric and young adult populations, with few effective therapeutic options available. Despite immunotherapy advancements, its efficacy in OS …
View article: Clofarabine monotherapy in aggressive, relapsed and refractory Langerhans cell histiocytosis
Clofarabine monotherapy in aggressive, relapsed and refractory Langerhans cell histiocytosis Open
Summary Over 50% of patients with systemic LCH are not cured with front‐line therapies, and data to guide salvage options are limited. We describe 58 patients with LCH who were treated with clofarabine. Clofarabine monotherapy was active a…
View article: SMARCA4 is a haploinsufficient B cell lymphoma tumor suppressor that fine-tunes centrocyte cell fate decisions
SMARCA4 is a haploinsufficient B cell lymphoma tumor suppressor that fine-tunes centrocyte cell fate decisions Open
SMARCA4 encodes one of two mutually exclusive ATPase subunits in the BRG/BRM associated factor (BAF) complex that is recruited by transcription factors (TFs) to drive chromatin accessibility and transcriptional activation. SMARCA4 is among…
View article: Durable immunity to EBV after rituximab and third-party LMP-specific T cells: a Children’s Oncology Group study
Durable immunity to EBV after rituximab and third-party LMP-specific T cells: a Children’s Oncology Group study Open
Posttransplant lymphoproliferative disease (PTLD) in pediatric solid organ transplant (SOT) recipients is characterized by uncontrolled proliferation of Epstein-Barr virus–infected (EBV+) B cells due to decreased immune function. This stud…
View article: Circulating senescent myeloid cells drive blood brain barrier breakdown and neurodegeneration
Circulating senescent myeloid cells drive blood brain barrier breakdown and neurodegeneration Open
Summary Neurodegenerative diseases (ND) are characterized by progressive loss of neuronal function. Mechanisms of ND pathogenesis are incompletely understood, hampering the development of effective therapies. Langerhans cell histiocytosis …
View article: Pediatric Swine Model of Methicillin-Resistant Staphylococcus aureus Sepsis-Induced Coagulopathy, Disseminated Microvascular Thrombosis, and Organ Injuries
Pediatric Swine Model of Methicillin-Resistant Staphylococcus aureus Sepsis-Induced Coagulopathy, Disseminated Microvascular Thrombosis, and Organ Injuries Open
CONTEXT: Sepsis-induced coagulopathy leading to disseminated microvascular thrombosis is associated with high mortality and has no existing therapy. Despite the high prevalence of Gram-positive bacterial sepsis, especially methicillin-resi…
View article: Alemtuzumab and CXCL9 levels predict likelihood of sustained engraftment after reduced-intensity conditioning HCT
Alemtuzumab and CXCL9 levels predict likelihood of sustained engraftment after reduced-intensity conditioning HCT Open
Overall survival after reduced-intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (HCT) using alemtuzumab, fludarabine, and melphalan is associated with high rates of mixed chimerism (MC) and secondary graft failure…
View article: Cellular distribution of mutations and association with disease risk in Langerhans cell histiocytosis without <i>BRAF</i>V600E
Cellular distribution of mutations and association with disease risk in Langerhans cell histiocytosis without <i>BRAF</i>V600E Open
Langerhans cell histiocytosis (LCH) is a histiocytic neoplasm primarily driven by activating mutations of MAPK pathway genes in hematopoietic and myeloid cells. 1-46][7][8][9] Other mutations include small deletions of BRAF, mutations of M…
View article: IFN-γ signature in the plasma proteome distinguishes pediatric hemophagocytic lymphohistiocytosis from sepsis and SIRS
IFN-γ signature in the plasma proteome distinguishes pediatric hemophagocytic lymphohistiocytosis from sepsis and SIRS Open
Hemophagocytic lymphohistiocytosis (HLH) is a syndrome characterized by pathologic immune activation in which prompt recognition and initiation of immune suppression is essential for survival. Children with HLH have many overlapping clinic…
View article: Defining the Inflammatory Plasma Proteome in Pediatric Hodgkin Lymphoma
Defining the Inflammatory Plasma Proteome in Pediatric Hodgkin Lymphoma Open
Hodgkin lymphoma (HL) histopathology is characterized by rare malignant Reed–Sternberg cells among an inflammatory infiltrate. We hypothesized that characteristics of inflammation in pediatric HL lesions would be reflected by the levels of…
View article: Suppressor of Cytokine Signaling-2 Gene Disruption Promotes ApcMin/+ Tumorigenesis and Activator Protein-1 Activation
Suppressor of Cytokine Signaling-2 Gene Disruption Promotes ApcMin/+ Tumorigenesis and Activator Protein-1 Activation Open
Epigenetic in vitro and in vivo studies suggest that suppressor of cytokine signaling-2 (SOCS2) may normally limit tumorigenesis in the intestine; however, this theory has not been directly tested. We hypothesized that SOCS2 deficiency pro…
View article: High-Fat Diet: Bacteria Interactions Promote Intestinal Inflammation Which Precedes and Correlates with Obesity and Insulin Resistance in Mouse
High-Fat Diet: Bacteria Interactions Promote Intestinal Inflammation Which Precedes and Correlates with Obesity and Insulin Resistance in Mouse Open
BackgroundObesity induced by high fat (HF) diet is associated with inflammation which contributes to development of insulin resistance. Most prior studies have focused on adipose tissue as the source of obesity-associated inflammation. Inc…
View article: Biochromoendoscopy: molecular imaging with capsule endoscopy for detection of adenomas of the GI tract
Biochromoendoscopy: molecular imaging with capsule endoscopy for detection of adenomas of the GI tract Open
Current capsule endoscopy (CE) provides minimally invasive technology for gastrointestinal imaging, but has limited ability to discriminate different polyp types. Near Infrared Fluorescent (NIRF) probes activated by biomarkers upregulated …
View article: Overcoming T-cell exhaustion in LCH: PD-1 blockade and targeted MAPK inhibition are synergistic in a mouse model of LCH
Overcoming T-cell exhaustion in LCH: PD-1 blockade and targeted MAPK inhibition are synergistic in a mouse model of LCH Open
Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplasia characterized by granulomatous lesions containing pathological CD207+ dendritic cells (DCs) with persistent MAPK pathway activation. Standard-of-care chemotherapies a…
View article: JAK/STAT pathway inhibition sensitizes CD8 T cells to dexamethasone-induced apoptosis in hyperinflammation
JAK/STAT pathway inhibition sensitizes CD8 T cells to dexamethasone-induced apoptosis in hyperinflammation Open
Cytokine storm syndromes (CSS) are severe hyperinflammatory conditions characterized by excessive immune system activation leading to organ damage and death. Hemophagocytic lymphohistiocytosis (HLH), a disease often associated with inherit…
View article: Circulating CD1c+ myeloid dendritic cells are potential precursors to LCH lesion CD1a+CD207+ cells
Circulating CD1c+ myeloid dendritic cells are potential precursors to LCH lesion CD1a+CD207+ cells Open
Key Points Transcriptional profile of LCH CD1a+CD207+ DCs is most closely related to that of CD1c+ mDCs in the blood. Lineage tracing with BRAFV600E and HLA-DQB2 expression supports CD1c+ mDCs as precursors to LCH CD1a+CD207+ DCs.
View article: CNS Langerhans cell histiocytosis: Common hematopoietic origin for LCH‐associated neurodegeneration and mass lesions
CNS Langerhans cell histiocytosis: Common hematopoietic origin for LCH‐associated neurodegeneration and mass lesions Open
BACKGROUND Central nervous system Langerhans cell histiocytosis (CNS‐LCH) brain involvement may include mass lesions and/or a neurodegenerative disease (LCH‐ND) of unknown etiology. The goal of this study was to define the mechanisms of pa…
View article: A genome-wide association study of LCH identifies a variant in SMAD6 associated with susceptibility
A genome-wide association study of LCH identifies a variant in SMAD6 associated with susceptibility Open
To the editor:
Langerhans cell histiocytosis (LCH) is a hematologic disorder that presents with a wide spectrum of symptoms, ranging from focal lesions to potentially lethal multiorgan disease, affecting 4 to 8 per million children per ye…
View article: Alternative genetic mechanisms of BRAF activation in Langerhans cell histiocytosis
Alternative genetic mechanisms of BRAF activation in Langerhans cell histiocytosis Open
Key Points A BRAF gene fusion and small in-frame BRAF deletions were found in a subset of LCH lesions lacking BRAF-V600E or MAP2K1 mutations. In LCH model systems, responses to MAPK pathway inhibitors depend on the specific genetic alterat…