Publications by authors named "Dale D"

The pancreas is a dual-function organ, with exocrine cells that aid in digestion and endocrine cells that regulate glucose homeostasis. These cell types share common progenitors and arise from the embryonic ducts. Early signaling events in the embryonic ducts shape the neonatal, adolescent, and adult exocrine and endocrine pancreas.

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  • A phase 3 trial was conducted to evaluate the efficacy and safety of mavorixafor, an oral medication, in individuals with WHIM syndrome, a rare immunodeficiency disorder caused by genetic mutations.
  • Participants were randomly assigned to receive either mavorixafor or a placebo for 52 weeks, with the study focusing on the time above certain white blood cell counts as the primary endpoint.
  • Results showed mavorixafor significantly increased white blood cell counts, reduced infection rates and severity, and was well tolerated without serious adverse events occurring during the study.
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  • - Severe chronic neutropenia leads to a low absolute neutrophil count, increasing the risk of bacterial infections, but can be treated effectively with G-CSF injections, raising questions about potential risks of further blood disorders.
  • - Research from the Severe Chronic Neutropenia International Registry indicates that while there are low risks of conditions like MDS or AML, certain patient groups may be more vulnerable.
  • - New oral treatments are being investigated as alternatives to G-CSF, including neutrophil elastase inhibitors and gene therapy, but their safety, effectiveness, and costs have yet to be fully evaluated.
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Background: Coinfection with malaria and typhoid fever is a major public health issue in developing countries. In endemic areas, including Ethiopia, people are at risk of acquiring both malaria and typhoid fever at the same time. Therefore, this study aimed to determine the magnitude of malaria-typhoid fever coinfection in febrile patients attending hospital at Southern Ethiopia.

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Background: Health promotion and disease prevention programme registries (HPPRs), also called 'best practice portals', serve as entry points and practical repositories that provide decision-makers with easy access to (evidence-based) practices. However, there is limited knowledge of differences or overlaps of howe current national HPPRs in Europe function, the context and circumstances in which these HPPRs were developed, and the mechanisms utilised by each HPPR for the assessment, classification and quality improvement of the included practices. This study prepared an overview of different approaches in several national HPPRs and the EU Best Practice Portal (EU BPP) as well as identified commonalities and differences among the core characteristics of the HPPRs.

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Neutropenia, as an isolated blood cell deficiency, is a feature of a wide spectrum of acquired or congenital, benign or premalignant disorders with a predisposition to develop myelodysplastic neoplasms/acute myeloid leukemia that may arise at any age. In recent years, advances in diagnostic methodologies, particularly in the field of genomics, have revealed novel genes and mechanisms responsible for etiology and disease evolution and opened new perspectives for tailored treatment. Despite the research and diagnostic advances in the field, real world evidence, arising from international neutropenia patient registries and scientific networks, has shown that the diagnosis and management of neutropenic patients is mostly based on the physicians' experience and local practices.

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Accurately counting analog events requires constructing an electronics chain that produces one count for each input pulse. In this work we review the use of Nuclear Instrumentation Module electronic units for counting neutron capture events in a He tube. We identify two unique types of false trigger events in a leading-edge discriminator and show how a dual timer module can be used to produce a veto window to exclude these events.

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Objective: There is a high prevalence of inadequate dose adjustment among inpatients with renal insufficiency worldwide. There is, however, a paucity of studies that summarizes the topic in the African context. Therefore, this study aims to summarize the prevalence of inappropriate drug dose adjustment (IDDA) and associated factors among inpatients with renal impairment in Africa.

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A pandemic of respiratory illnesses from a novel coronavirus known as Sars-CoV-2 has swept across the globe since December of 2019. This is calling upon the research community including medical imaging to provide effective tools for use in combating this virus. Research in biomedical imaging of viral patients is already very active with machine learning models being created for diagnosing Sars-CoV-2 infections in patients using CT scans and chest x-rays.

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Heterozygous mutations in , the gene for neutrophil elastase, cause cyclic and congenital neutropenia through the programed cell death of neutrophil progenitors in the bone marrow. Granulocyte colony-stimulating factor is an effective therapy for these diseases, but alternative therapies are needed, especially for patients who do not respond well or are at high risk of developing myeloid malignancies. We developed an HL60 cell model for neutropenia and previously demonstrated that transient and regulated expression of mutant causes cell death by accelerated apoptosis.

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Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome (WS) is a combined immunodeficiency caused by gain-of-function mutations in the C-X-C chemokine receptor type 4 (CXCR4) gene. We characterize a unique international cohort of 66 patients, including 57 (86%) cases previously unreported, with variable clinical phenotypes. Of 17 distinct CXCR4 genetic variants within our cohort, 11 were novel pathogenic variants affecting 15 individuals (23%).

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Severe congenital neutropenia (SCN) is a life-threatening marrow failure disorder, usually caused by heterozygous mutations in . Potential genetic treatment strategies include biallelic knockout or gene correction via homology-directed repair (HDR). Such strategies, however, involve the potential loss of the essential function of the normal allele product or limited coverage of diverse monogenic mutations within the patient population, respectively.

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Purpose: We evaluated the incidence of febrile neutropenia (FN) and related clinical outcomes among patients treated with myelosuppressive chemotherapy for nonmyeloid malignancies who received pegfilgrastim on-body injector (OBI) or other options (Other) for FN prophylaxis.

Methods: In this prospective observational study, adult patients with breast, prostate, or lung cancer, or non-Hodgkin lymphoma at risk for FN were stratified into subgroups based on FN prophylaxis used in the first chemotherapy cycle: pegfilgrastim OBI vs Other (pegfilgrastim or biosimilar pegfilgrastim prefilled syringe, daily filgrastim, or no granulocyte colony-stimulating factor [G-CSF]) for up to 4 planned chemotherapy cycles.

Results: This US study enrolled 2575 eligible patients (OBI, 1624; Other, 951).

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  • * The study gathered data from over 16,000 patient-years and found that complications depend on the cause of SCN, with conditions like myelodysplasia (MDS) and acute myeloid leukemia (AML) appearing mostly in congenital cases.
  • * Overall, the report indicates that patients with chronic autoimmune/idiopathic neutropenia generally have a favorable prognosis, and long-term G-CSF treatment doesn't significantly increase risks for serious complications
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Background: Breast cancer chemotherapy often carries a high risk of febrile neutropenia (FN); guidelines recommend prophylaxis with granulocyte colony-stimulating factor (G-CSF), such as pegfilgrastim. Neulasta Onpro on-body injector (OBI) is a delivery device administering pegfilgrastim approximately 27 h after application.

Methods: This prospective study examined patients with breast cancer who received chemotherapy with a high risk of FN, receiving OBI ("OBI") or other options (other G-CSF or none; "other").

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Evidence-based US guidelines provide recommendations for the use of granulocyte colony-stimulating factor (G-CSF) as supportive therapy in patients with cancer receiving chemotherapy. Pegfilgrastim is recommended for FN prophylaxis in patients with non-myeloid malignancies receiving a high-risk chemotherapy regimen, or an intermediate-risk regimen if one or more risk factors are present. The guidelines highlight the patient characteristics and chemotherapy regimens for solid tumors and hematologic malignancies that may influence a patient's overall risk of FN and may benefit from pegfilgrastim support.

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  • * Researchers found specific mutations in the CLPB gene associated with this condition that impact protein folding and mitochondrial function, though some expected symptoms were not present in the cases studied.
  • * The presence of these mutations affects the differentiation of blood cells and leads to increased cell death, suggesting CLPB variants should be considered when diagnosing congenital neutropenia.
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To understand the mechanisms that mediate germline genetic leukemia predisposition, we studied the inherited ribosomopathy Shwachman-Diamond syndrome (SDS), a bone marrow failure disorder with high risk of myeloid malignancies at an early age. To define the mechanistic basis of clonal hematopoiesis in SDS, we investigate somatic mutations acquired by patients with SDS followed longitudinally. Here we report that multiple independent somatic hematopoietic clones arise early in life, most commonly harboring heterozygous mutations in EIF6 or TP53.

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The burden of chronic disease in Europe continues to grow. A major challenge facing national governments is how to tackle the risk factors of sedentary lifestyle, alcohol abuse, smoking, and unhealthy diet. These factors are complex and necessitate intersectoral collaboration to strengthen health promotion, counter-act the social determinants of health, and reduce the prevalence of chronic disease.

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  • WHIM syndrome is a rare immunodeficiency linked to mutations in the CXCR4 gene, affecting immune functions such as white blood cell mobilization.
  • A phase 2 study tested mavorixafor, an oral medication that targets the CXCR4 receptor, on 8 adult patients, showing it was well tolerated with no severe side effects.
  • Results indicated significant increases in white blood cell counts and a reduction in infections and warts, suggesting mavorixafor could be beneficial for long-term treatment in WHIM syndrome patients.
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The explicit breaking of the axial symmetry by quantum fluctuations gives rise to the so-called axial anomaly. This phenomenon is solely responsible for the decay of the neutral pion π into two photons (γγ), leading to its unusually short lifetime. We precisely measured the decay width Γ of the [Formula: see text] process.

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Background: The frequency of neutropenia in pediatric primary immunodeficiency disorders (PIDDs) is unknown and potentially underappreciated. Our study aimed to determine the overall frequency and severity of neutropenia in children diagnosed with a PIDD entered in the United States Immunodeficiency Network (USIDNET) patient registry.

Procedure: Neutropenia data and demographic/clinical information from 1145 patients younger than 21 years of age was obtained from the USIDNET registry.

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