Context: Pituitary blastoma is a rare, dysontogenetic hypophyseal tumor of infancy first described in 2008, strongly suggestive of DICER1 syndrome.
Objective: This work aims to describe genetic alterations, clinical courses, outcomes, and complications in all known pituitary blastoma cases.
Design And Setting: A multi-institutional case series is presented from tertiary pediatric oncology centers.
J Am Coll Cardiol
November 2020
Venous thromboembolism (VTE), composed of pulmonary embolism and deep venous thrombosis, is a significant cause of maternal mortality in the developed world. Normal physiological changes of pregnancy increase coagulability, which is compounded by patient-inherited and acquired risk factors. Depending on these risks and peripartum stage, the benefits of thromboprophylaxis can outweigh potential side effects.
View Article and Find Full Text PDFVariation in age at maturity is an important contributor to life history and demographic variation within and among species. The optimal age at maturity can vary by sex, and the ability of each sex to evolve towards its fitness optimum depends on the genetic architecture of maturation. Using GWAS of RAD sequencing data, we show that age at maturity in Chinook salmon exhibits sex-specific genetic architecture, with age at maturity in males influenced by large (up to 20 Mb) male-specific haplotypes.
View Article and Find Full Text PDFObjective: To describe prenatal and postpartum consumption of water, cows' milk, 100 % juice and sugar-sweetened beverages (SSB) among women enrolled in the Special Supplemental Nutrition Program for Women, Infants and Children (WIC) programme in New York City (NYC) and to identify correlates of SSB intake in this population.
Design: Cross-sectional data were collected from structured questionnaires that included validated beverage frequency questionnaires with the assistance of container samples. The association of maternal and household factors and non-SSB consumption with habitual daily energetic (kJ (kcal)) intake from SSB was assessed by using multivariable median regression.
Background: Covid-19 testing and disease outcomes according to demographic and neighborhood characteristics must be understood.
Methods: Using aggregate administrative data from a multi-site academic healthcare system in New York from March 1 - May 14, 2020, we examined patient demographic and neighborhood characteristics according to Covid-19 testing and disease outcomes.
Results: Among the 23,918 patients, higher proportions of those over 65 years old, male sex, Hispanic ethnicity, Medicare, or Medicaid insurance had positive tests, were hospitalized, or died than those with younger age, non-Hispanic ethnicity, or private insurance.
Phenotypic testing for drug susceptibility of is critical to basic research and managing the evolving problem of antimicrobial resistance in tuberculosis management, but it remains a specialized technique to which access is severely limited. Here, we report on the development and validation of an improved phage-mediated detection system for We incorporated a nanoluciferase (Nluc) reporter gene cassette into the TM4 mycobacteriophage genome to create phage TM4-nluc. We assessed the performance of this reporter phage in the context of cellular limit of detection and drug susceptibility testing using multiple biosafety level 2 drug-sensitive and -resistant auxotrophs as well as virulent strains.
View Article and Find Full Text PDFPurpose: Closed eye neutrophils have demonstrated increased prevalence in dry eye disease, but the phenotype and extent of activation of these cells has yet to be described.
Methods: 12 normal subjects and 12 subjects with dry eye disease were recruited and trained for self-collection of closed eye leukocytes, immediately upon awakening. Tear leukocytes were isolated and peripheral blood was collected, and stained with a panel of fluorescently-labeled antibodies to determine the activation phenotype of neutrophils.
Euthanasia is a necessary component in research and must be conducted humanely. Currently, regulated CO₂ exposure in conscious rats is acceptable, but data are divided on whether CO₂ alone is more distressing than anesthesia prior to CO₂. To evaluate distress in rats, we compared physiologic responses to CO₂ euthanasia with and without isoflurane preanesthesia.
View Article and Find Full Text PDFPurpose: The safety of KPI-121 0.25%, an ophthalmic nanoparticle suspension of loteprednol etabonate, was evaluated in subjects with dry eye disease (DED) in one phase 2 and three phase 3 randomized trials of similar design.
Methods: Adults with DED received KPI-121 0.
De novo mutations (DNMs) are increasingly recognized as rare disease causal factors. Identifying DNM carriers will allow researchers to study the likely distinct molecular mechanisms of DNMs. We developed Famdenovo to predict DNM status (DNM or familial mutation [FM]) of deleterious autosomal dominant germline mutations for any syndrome.
View Article and Find Full Text PDFRelapse of acute lymphoblastic leukemia (ALL) remains a leading cause of childhood death. Prior studies have shown clonal mutations at relapse often arise from relapse-fated subclones that exist at diagnosis. However, the genomic landscape, evolutionary trajectories and mutational mechanisms driving relapse are incompletely understood.
View Article and Find Full Text PDFInvariant natural killer T (iNKT) cells are innate-like T lymphocytes characterized by the expression of an invariant T cell receptor (iTCR) that recognizes glycolipid antigens presented by the MHC I-like CD1d molecule. Following antigenic stimulation, iNKT cells rapidly produce large amounts of cytokines that can trans-activate dendritic cells (DC) and promote the anti-tumor functions of cytotoxic lymphocytes, such as natural killer (NK) and CD8 T cells. Additionally, iNKT cells can mediate robust and direct cytotoxicity against CD1d tumor targets.
View Article and Find Full Text PDFBackground: Asynchrony has been reported to be a marker of ischemic-induced left ventricular dysfunction, the magnitude of which correlates with extent of epicardial coronary disease. We wished to determine whether normal-appearing arterial territories with mild degrees of asynchrony have lower Rb PET absolute myocardial blood flow (MBF) and/or lower myocardial flow reserve (MFR).
Methods And Results: Data were examined retrospectively for 105 patients evaluated for known/suspected CAD who underwent rest/regadenoson-stress Rb PET/CT and quantitative coronary angiography.
Dry eye affects millions of individuals. In experimental models, dry eye disease is associated with T helper cell 17-mediated inflammation of the ocular surface that may cause persistent damage to the corneal epithelium. However, the initiating and perpetuating factors associated with chronic inflammation of the ocular surface remain unclear.
View Article and Find Full Text PDFCancer risk is highly variable in carriers of the common R337H founder allele, possibly due to the influence of modifier genes. Whole-genome sequencing identified a variant in the tumor suppressor (E134*/Glu134Ter/rs146752602) in a subset of R337H carriers. Haplotype-defining variants were verified in 203 patients with cancer, 582 relatives, and 42,438 newborns.
View Article and Find Full Text PDFProphylactic donor lymphocyte infusions (DLI) are used to augment post-transplant immune recovery to reduce both infectious complications and disease recurrence. Preclinical studies implicate the naive T-cell subset as the primary driver of graft-versus-host disease (GvHD). In this phase I dose escalation study, we assessed the safety of a DLI that was depleted of CD45RA+ naive T cells.
View Article and Find Full Text PDFGain of function variants in SAMD9 cause MIRAGE syndrome, a rare Mendelian disorder that results in myeloid dysplastic syndrome (MDS), poor immune response, restricted growth, adrenal insufficiency, ambiguous genitalia, feeding difficulties and most often significantly reduced lifespan. In this study, we describe histomorphologic and genetic changes occurring in serial bone marrow measurements in a patient with MIRAGE syndrome and untreated MDS of 9 years. Histomorphological analysis during childhood showed progressive hypocellularity with erythroid and megakaryocytic dysplasia and cytogenetic testing demonstrated monosomy 7.
View Article and Find Full Text PDFJuvenile xanthogranuloma (JXG) usually presents with lesions isolated to the skin; however, aggressive, disseminated forms also occur. Identification of a novel fusion in a child with JXG guided targeted therapy with dasatinib, leading to a dramatic response.
View Article and Find Full Text PDFThe SARS-CoV-2 pandemic has created an unprecedented need for rapid diagnostic testing to enable the efficient treatment and mitigation of COVID-19. The primary diagnostic tool currently employed is reverse transcription polymerase chain reaction (RT-PCR), which can have good sensitivity and excellent specificity. Unfortunately, implementation costs and logistical problems with reagents during the global SARS-CoV-2 pandemic have hindered its universal on demand adoption.
View Article and Find Full Text PDFAims: Several morphologically overlapping (myo)fibroblastic neoplasms harbour USP6 fusions, including aneurysmal bone cysts, nodular fasciitis, myositis ossificans, cranial fasciitis, fibro-osseous pseudotumour of the digits, and cellular fibroma of the tendon sheath. USP6-induced neoplasms are almost universally benign and cured by local excision. We aim to highlight the diagnostic value of USP6 fusion detection in a series of aggressive-appearing paediatric myofibroblastic tumours.
View Article and Find Full Text PDFInvariant natural killer T cells (iNKTs) directly kill tumor cells and trans-activate the anti-tumor functions of dendritic cells (DC), natural killer (NK) cells, and T and B cells. As such, iNKTs serve as a powerful tool for use in cell-based cancer immunotherapy. iNKT cell activation commonly requires engagement of the invariant T cell receptor (iTCR) by CD1d presenting glycolipid antigens.
View Article and Find Full Text PDFCytokine 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 inherited defects in cell-mediated cytotoxicity, serves as a prototypical CSS for which the 5-year survival is only 60%. Frontline therapy for HLH consists of the glucocorticoid dexamethasone (DEX) and the chemotherapeutic agent etoposide.
View Article and Find Full Text PDF