The latest medical research on General Medicine / Internal Medicine

The research magnet gathers the latest research from around the web, based on your specialty area. Below you will find a sample of some of the most recent articles from reputable medical journals about general medicine / internal medicine gathered by our medical AI research bot.

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Critical requirement for BCR, BAFF, and BAFFR in memory B cell survival.

J Exp Med

Memory B cells (MBCs) are long-lived cells that form a critical part of immunological memory, providing rapid antibody responses to recurring infec...

BAFFR controls early memory B cell responses but is dispensable for germinal center function.

J Exp Med

The TNF superfamily ligand BAFF maintains the survival of naive B cells by signaling through its surface receptor, BAFFR. Activated B cells maintai...

Supervised Machine Learning Applied to Automate Flash and Prolonged Capillary Refill Detection by Pulse Oximetry.

Frontiers in Physiology

Develop an automated approach to detect flash (<1.0 s) or prolonged (>2.0 s) capillary refill time (CRT) that correlates with clinician judgment by applying several supervised machine learning (ML) techniques to pulse oximeter plethysmography data.

Data was collected in the Pediatric Intensive Care Unit (ICU), Cardiac ICU, Progressive Care Unit, and Operating Suites in a large academic children's hospital. Ninety-nine children and 30 adults were enrolled in testing and validation cohorts, respectively. Patients had 5 paired CRT measurements by a modified pulse oximeter device and a clinician, generating 485 waveform pairs for model training. Supervised ML models using gradient boosting (XGBoost), logistic regression (LR), and support vector machines (SVMs) were developed to detect flash (<1 s) or prolonged CRT (≥2 s) using clinician CRT assessment as the reference standard. Models were compared using Area Under the Receiver Operating Curve (AUC) and precision-recall curve (positive predictive value vs. sensitivity) analysis. The best performing model was externally validated with 90 measurement pairs from adult patients. Feature importance analysis was performed to identify key waveform characteristics.

For flash CRT, XGBoost had a greater mean AUC (0.79, 95% CI 0.75-0.83) than logistic regression (0.77, 0.71-0.82) and SVM (0.72, 0.67-0.76) models. For prolonged CRT, XGBoost had a greater mean AUC (0.77, 0.72-0.82) than logistic regression (0.73, 0.68-0.78) and SVM (0.75, 0.70-0.79) models. Pairwise testing showed statistically significant improved performance comparing XGBoost and SVM; all other pairwise model comparisons did not reach statistical significance. XGBoost showed good external validation with AUC of 0.88. Feature importance analysis of XGBoost identified distinct key waveform characteristics for flash and prolonged CRT, respectively.

Novel application of supervised ML to pulse oximeter waveforms yielded multiple effective models to identify flash and prolonged CRT, using clinician judgment as the reference standard.

Supervised machine learning applied to pulse oximeter waveform features predicts flash or prolonged capillary refill.

Deep Learning Algorithm Classifies Heartbeat Events Based on Electrocardiogram Signals.

Frontiers in Physiology

Cardiovascular diseases (CVDs) have become the number 1 threat to human health. Their numerous complications mean that many countries remain unable...

Turbulent Systolic Flow Downstream of a Bioprosthetic Aortic Valve: Velocity Spectra, Wall Shear Stresses, and Turbulent Dissipation Rates.

Frontiers in Physiology

Every year, a quarter million patients receive prosthetic heart valves in aortic valve replacement therapy. Prosthetic heart valves are known to le...

Circular RNAs in Cardiac Regeneration: Cardiac Cell Proliferation, Differentiation, Survival, and Reprogramming.

Frontiers in Physiology

Circular RNAs (circRNAs) are classified as long non-coding RNAs (lncRNAs) that are characterized by a covalent closed-loop structure. This closed-l...

An Understandable, Extensible, and Reusable Implementation of the Hodgkin-Huxley Equations Using Modelica.

Frontiers in Physiology

The Hodgkin-Huxley model of the squid giant axon has been used for decades as the basis of many action potential models. These models are usually c...

Metabolic Physiological Networks: The Impact of Age.

Frontiers in Physiology

Metabolic homeostasis emerges from the interplay between several feedback systems that regulate the physiological variables related to energy expen...

Sustained androgen receptor signaling is a determinant of melanoma cell growth potential and tumorigenesis.

J Exp Med

Melanoma susceptibility differs significantly in male versus female populations. Low levels of androgen receptor (AR) in melanocytes of the two sex...

Somatic Mutations in UBA1 and Severe Adult-Onset Autoinflammatory Disease.

N Engl J

Adult-onset inflammatory syndromes often manifest with overlapping clinical features. Variants in ubiquitin-related genes, previously implicated in autoinflammatory disease, may define new disorders.

We analyzed peripheral-blood exome sequence data independent of clinical phenotype and inheritance pattern to identify deleterious mutations in ubiquitin-related genes. Sanger sequencing, immunoblotting, immunohistochemical testing, flow cytometry, and transcriptome and cytokine profiling were performed. CRISPR-Cas9-edited zebrafish were used as an in vivo model to assess gene function.

We identified 25 men with somatic mutations affecting methionine-41 (p.Met41) in UBA1, the major E1 enzyme that initiates ubiquitylation. (The gene UBA1 lies on the X chromosome.) In such patients, an often fatal, treatment-refractory inflammatory syndrome develops in late adulthood, with fevers, cytopenias, characteristic vacuoles in myeloid and erythroid precursor cells, dysplastic bone marrow, neutrophilic cutaneous and pulmonary inflammation, chondritis, and vasculitis. Most of these 25 patients met clinical criteria for an inflammatory syndrome (relapsing polychondritis, Sweet's syndrome, polyarteritis nodosa, or giant-cell arteritis) or a hematologic condition (myelodysplastic syndrome or multiple myeloma) or both. Mutations were found in more than half the hematopoietic stem cells, including peripheral-blood myeloid cells but not lymphocytes or fibroblasts. Mutations affecting p.Met41 resulted in loss of the canonical cytoplasmic isoform of UBA1 and in expression of a novel, catalytically impaired isoform initiated at p.Met67. Mutant peripheral-blood cells showed decreased ubiquitylation and activated innate immune pathways. Knockout of the cytoplasmic UBA1 isoform homologue in zebrafish caused systemic inflammation.

Using a genotype-driven approach, we identified a disorder that connects seemingly unrelated adult-onset inflammatory syndromes. We named this disorder the VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome. (Funded by the NIH Intramural Research Programs and the EU Horizon 2020 Research and Innovation Program.).

Nfkb2 variants reveal a p100-degradation threshold that defines autoimmune susceptibility.

J Exp Med

NF-κB2/p100 (p100) is an inhibitor of κB (IκB) protein that is partially degraded to produce the NF-κB2/p52 (p52) transcription factor. Heterozygou...