A Multianalyte Machine Learning Model to Detect Wrong Blood in Complete Blood Count Tube Errors in a Pediatric Setting.

Background: Multianalyte machine learning (ML) models can potentially identify previously undetectable wrong blood in tube (WBIT) errors, improving upon current single-analyte delta check methodology. However, WBIT detection model performance has not been assessed in a real-world, low-prevalence context. To estimate real-world positive predictive values, we propose a methodology to assess WBIT detection models by evaluating the impact of missing data and by using a "low prevalence" validation data set.

Missense variants weakening a SOX9 phosphodegron linked to odontogenesis defects, scoliosis and other skeletal features.

SOX9 encodes an SRY-related transcription factor critical for chondrogenesis and sex determination among other processes. Loss-of-function variants cause campomelic dysplasia and Pierre Robin Sequence, while both gain- and loss-of-function variants cause disorders of sex development. SOX9 has also been linked to scoliosis and cancers, but variants are undetermined.

Novel Computational and Artificial Intelligence Models in Cancer Research.

The ICIBM 2023 marked the 11th annual conference of its kind, with the ICIBM recently becoming the official conference of the International Association for Intelligent Biology and Medicine (IAIBM), showcasing cutting-edge advancements at the intersection of computation and biomedical research [...

Molecular Basis of Oncogenic PI3K Proteins.

The dysregulation of phosphatidylinositol 3-kinase (PI3K) signaling plays a pivotal role in driving neoplastic transformation by promoting uncontrolled cell survival and proliferation. This oncogenic activity is primarily caused by mutations that are frequently found in PI3K genes and constitutively activate the PI3K signaling pathway. However, tumorigenesis can also arise from nonmutated PI3K proteins adopting unique active conformations, further complicating the understanding of PI3K-driven cancers.

Integrated Local and Systemic Communication Factors Regulate Nascent Hematopoietic Progenitor Escape During Developmental Hematopoiesis.

Mammalian blood cells originate from specialized 'hemogenic' endothelial (HE) cells in major arteries. During the endothelial-to-hematopoietic transition (EHT), nascent hematopoietic stem cells (HSCs) bud from the arterial endothelial wall and enter circulation, destined to colonize the fetal liver before ultimately migrating to the bone marrow. Mechanisms and processes that facilitate EHT and the release of nascent HSCs are incompletely understood, but may involve signaling from neighboring vascular endothelial cells, stromal support cells, circulating pre-formed hematopoietic cells, and/or systemic factors secreted by distal organs.

Clinical features associated with self-reported food insecurity in people with cystic fibrosis.

Background: Food insecurity (FI) is more prevalent in people with cystic fibrosis (PwCF) than the reported national prevalence, but there are limited data on the relationship between FI and health outcomes in PwCF. The objective of this study was to analyze the relationship between FI in PwCF and pulmonary and nutritional status.

Methods: We leveraged an electronic cross-sectional survey that ascertained FI status and gave participants the option to link their survey data to their records in the Cystic Fibrosis Foundation Patient Registry (CFFPR).

Frontal Paraventricular Cysts: Refined Definitions and Outcomes.

Background And Purpose: Frontal paraventricular cystic changes have a varied etiology that includes connatal cysts, subependymal pseudocysts, necrosis, and enlarged perivascular spaces. These may be difficult to distinguish by neuroimaging and have a variety of associated prognoses. We aim to refine the neuroimaging definition of frontal horn cysts and correlate it with adverse clinical conditions.

The Bethesda System for Reporting Thyroid Cytopathology: Risk of Malignancy in Pediatric Thyroid Nodules.

Introduction: Thyroid nodules are infrequent findings in children, though malignancy rates are higher in this population. The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) standardizes the reporting of thyroid fine needle aspiration (FNA) specimens and has become a global reference for assessing the risk of malignancy (ROM) of thyroid nodules. The 2023 update includes pediatric-specific risk predictions and management recommendations.

In utero progression of cephaloceles: prenatal to postnatal analysis.

Objective: The natural history of cephaloceles is not well understood. The goal of this study was to better understand the natural history of fetal cephaloceles from prenatal diagnosis to the postnatal period.

Methods: Between January 2013 and April 2023, all patients evaluated with a cephalocele at the Center for Fetal Diagnosis and Treatment were identified.

Enhancing semantical text understanding with fine-tuned large language models: A case study on Quora Question Pair duplicate identification.

Semantical text understanding holds significant importance in natural language processing (NLP). Numerous datasets, such as Quora Question Pairs (QQP), have been devised for this purpose. In our previous study, we developed a Siamese Convolutional Neural Network (S-CNN) that achieved an F1 score of 82.

Multiomics dissection of human RAG deficiency reveals distinctive patterns of immune dysregulation but a common inflammatory signature.

Human recombination-activating gene (RAG) deficiency can manifest with distinct clinical and immunological phenotypes. By applying a multiomics approach to a large group of -mutated patients, we aimed at characterizing the immunopathology associated with each phenotype. Although defective T and B cell development is common to all phenotypes, patients with hypomorphic variants can generate T and B cells with signatures of immune dysregulation and produce autoantibodies to a broad range of self-antigens, including type I interferons.

Development and Validation of a Brief Age-Normed Screening Tool for Subthreshold Psychosis Symptoms in Youth.

Background And Hypothesis: Improvements in screening tools for early subthreshold psychosis symptoms are needed to facilitate early identification and intervention efforts, especially given the challenges of rapidly differentiating age-appropriate experiences from potential early signs of emerging psychosis. Tools can be lengthy and time-consuming, impacting their utility and accessibility across clinical settings, and age-normed data are limited. To address this gap, we sought to develop and validate a brief, empirically derived, age-normed, subthreshold psychosis screening tool, for public use.

Moving Beyond Static, Individualistic Approaches to Agency: Theories of Agency for Medical Education Researchers: AMEE Guide No. 177.

Agency - the capacity to produce an effect - is a foundational aspect of medical education. Agency is usually conceptualized at the level of the , with each learner charged with taking responsibility to pull themselves up by their bootstraps. This conceptualization is problematic.

Intelligent biology and medicine: Accelerating innovative computational approaches.

In this editorial, we summarize the 2023 International Conference on Intelligent Biology and Medicine (ICIBM 2023) conference which was held on July 16-19, 2023 in Tampa, Florida, USA. We then briefly describe the nine research articles included in this special issue. ICIBM 2023 scientific program included four tutorials and workshops, four keynote lectures, four eminent scholars' presentations, 11 concurrent scientific sessions, and a poster session.

Functional genotype classification groups distinguish disease severity in recessive dystrophic epidermolysis bullosa.

Recessive dystrophic epidermolysis bullosa (RDEB) is a genetic disorder due to pathogenic variants in the COL7A1 gene. In this study we determined the association between different categories of COL7A1 variants and clinical disease severity in 236 RDEB patients in North America. Published reports or in-silico predictions were used to assess the impact of pathogenic variants in COL7A1 on type VII collagen (C7) protein function.

Thromboembolic Risk in Juvenile Dermatomyositis Patients Treated With Intravenous Immunoglobulin.

This single-institution retrospective cohort study evaluates the risk of thromboembolic events (TE) in patients with juvenile dermatomyositis (JDM) treated with intravenous immunoglobulin (IVIg). We found no difference in the occurrence of TE in JDM patients treated with IVIg as compared to those without IVIg exposure; both cohorts had no TEs. Patients in both JDM cohorts had matched levels of other clotting risk factors, such as periods of limited mobility and hormonal contraceptive use.

Identification of a Subpopulation of Astrocyte Progenitor Cells in the Neonatal Subventricular Zone: Evidence that Migration is Regulated by Glutamate Signaling.

In mice engineered to express enhanced green fluorescent protein (eGFP) under the control of the entire glutamate transporter 1 (GLT1) gene, eGFP is found in all 'adult' cortical astrocytes. However, when 8.3 kilobases of the human GLT1/EAAT2 promoter is used to control expression of tdTomato (tdT), tdT is only found in a subpopulation of these eGFP-expressing astrocytes.

Bone marrow transplantation reverses metabolic alterations in multiple sulfatase deficiency: a case series.

Background: Multiple sulfatase deficiency (MSD) is an exceptionally rare neurodegenerative disorder due to the absence or deficiency of 17 known cellular sulfatases. The activation of all these cellular sulfatases is dependent on the presence of the formylglycine-generating enzyme, which is encoded by the SUMF1 gene. Disease-causing homozygous or compound heterozygous variants in SUMF1 result in MSD.

Immunogenomic determinants of exceptional response to immune checkpoint inhibition in renal cell carcinoma.

Immune checkpoint inhibitors can lead to 'exceptional', durable responses in a subset of persons. However, the molecular basis of exceptional response (ER) to immunotherapy in metastatic clear cell renal cell carcinoma (mccRCC) has not been well characterized. Here we analyzed pretherapy genomic and transcriptomic data in treatment-naive persons with mccRCC treated with standard-of-care immunotherapies: (1) combination of programmed cell death protein and ligand 1 (PD1/PDL1) and cytotoxic T lymphocyte-associated protein 4 inhibitors (IO/IO) or (2) combination of PD1/PDL1 and vascular endothelial growth factor (VEGF) receptor inhibitors (IO/VEGF).

UW supplementation with AP39 improves liver viability following static cold storage.

Static cold storage of donor livers at 4 °C incompletely arrests metabolism, ultimately leading to decreases in ATP levels, oxidative stress, cell death, and organ failure. Hydrogen Sulfide (HS) is an endogenously produced gas, previously demonstrated to reduce oxidative stress, reduce ATP depletion, and protect from ischemia and reperfusion injury. HS is difficult to administer due to its rapid release curve, resulting in cellular death at high concentrations.

Circle of Willis Variants and Their Association with Outcome after Successful Revascularization of Anterior Large Vessel Occlusion.

Background And Purpose: Leptomeningeal collaterals have been associated with better outcomes in large-vessel stroke, but little is known about how the Circle of Willis (CoW) collaterals affect stroke outcomes. We aimed to determine the relationship between three anatomically distinct CoW subtypes and 90-day outcomes in acute ischemic stroke patients after successful revascularization via endovascular thrombectomy (EVT).

Materials And Methods: We performed a retrospective analysis of patients treated with successful EVT for large-vessel occlusion at a comprehensive stroke center between May 2016 and November 2023.

Towards a Provider Builder Maturity Model to Empower Clinicians to Actively Participate in Electronic Health Record Design.

Background: Engagement of clinicians who understand clinical workflows and technology constraints can accelerate the development and implementation of better electronic health record (EHR) designs that improve quality and reduce burnout. Provider builder programs can accelerate clinical informatics education for a broader coalition of clinical specialties.

Objective: In this State of the Art / Best Practice paper, we aim to (1) propose a provider builder maturity model informed by the experience of three institutions using a single EHR vendor (Epic Systems©) and (2) describe the program elements and relationships necessary to advance along this model to yield organizational benefits.

Measurement of urine calcium, magnesium and phosphate: Preanalytical considerations in the elimination of the acidification step.

Background: Traditionally, urine analysis of calcium (Ca), magnesium (Mg) and phosphate (Phos) requires acidification of the sample. This study aims to assess the need for acidification and evaluate preanalytical factors that influence the accurate measurement of these analytes in urine.

Results: A total of 107 spot urine samples from patients with a median age of 9 years (95% ≤ 21 years of age, range 5 days to 46 years) were analyzed for Ca (n = 94), Mg (n = 97), and Phos (n = 102) with and without acidification.