The unnecessary use of short tandem repeat testing on bone marrow samples in patients after 1 year following allogeneic hematopoietic stem cell transplant.

Objectives: To determine whether the information provided by short tandem repeat (STR) testing and bone marrow (BM) biopsy specimens following hematopoietic stem cell transplant (HSCT) provides redundant information, leading to test overutilization, without additional clinical benefit.

Methods: Cases with synchronous STR and flow cytometric immunophenotyping (FCI) testing, as part of the BM evaluation, were assessed for STR/FCI concordance.

Results: Of 1199 cases (410 patients), we found the overall concordance between STR and FCI was 93%, with most cases (1063) classified as STR-/FCI-.

Reduced Levels of Lagging Strand Polymerases Shape Stem Cell Chromatin.

Stem cells display asymmetric histone inheritance while non-stem progenitor cells exhibit symmetric patterns in the male germline lineage. Here, we report that components involved in lagging strand synthesis, such as DNA polymerase α and δ (Polα and Polδ), have significantly reduced levels in stem cells compared to progenitor cells. Compromising Polα genetically induces the replication-coupled histone incorporation pattern in progenitor cells to be indistinguishable from that in stem cells, which can be recapitulated using a Polα inhibitor in a concentration-dependent manner.

A RETROSPECTIVE EVALUATION OF MORBIDITY AND MORTALITY IN ASSOCIATION WITH INFESTATION BY THE MITE IN AN AVIARY-HOUSED POPULATION OF GOULDIAN FINCHES ().

The Rhynonyssid mesostigmatic mite, , is a well-documented endoparasitic hematophagous arthropod of the respiratory tracts of multiple avian species, particularly Estrildid finches and canaries. In this retrospective study, 175 medical and 278 pathology records for the Gouldian finch () population (N = 377) at the San Diego Zoo between 2013 and 2021 were analyzed to evaluate the effectiveness of ivermectin-based prophylaxis. A multivariable negative binomial regression model was constructed to evaluate the population effects of monthly treatments on morbidity or mortality associated with respiratory mites.

Comparison Between REVEAL Lite 2 and COMPERA 2.0 for Risk Stratification in Pulmonary Arterial Hypertension.

Background: Risk stratification is the cornerstone of the management of pulmonary arterial hypertension (PAH). Current European Society of Cardiology/European Respiratory Society guidelines recommend using the Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA) three-strata risk model at baseline and the COMPERA 2.0 four-strata model at follow-up.

Development and Clinical Performance of InteliSwab COVID-19 Rapid Test: Evaluation of Antigen Test for the Diagnosis of SARS-CoV-2 and Analytical Sensitivity to Detect Variants of Concern Including Omicron and Subvariants.

Background And Objectives: Timely detection of SARS-CoV-2 infection with subsequent contact tracing and rapid isolation are considered critical to containing the pandemic, which continues with the emergence of new variants. Hence, there is an ongoing need for reliable point-of-care antigen rapid diagnostic tests (Ag-RDT). This report describes the development, evaluation, and analytical sensitivity of the diagnostic performance of the InteliSwab COVID-19 Rapid Test.

Aclarubicin stimulates RNA polymerase II elongation at closely spaced divergent promoters.

Anthracyclines are a class of widely prescribed anticancer drugs that disrupt chromatin by intercalating into DNA and enhancing nucleosome turnover. To understand the molecular consequences of anthracycline-mediated chromatin disruption, we used Cleavage Under Targets and Tagmentation (CUT&Tag) to profile RNA polymerase II during anthracycline treatment in cells. We observed that treatment with the anthracycline aclarubicin leads to elevated levels of RNA polymerase II and changes in chromatin accessibility.

Red blood cell distribution width to platelet ratio in neonatal foals with sepsis.

Background: Rapid and accurate markers to aid diagnosis of sepsis are needed in neonatal foals. The CBC variable red blood cell distribution width (RDW) to platelet ratio (RPR) is associated with inflammatory response and linked to poor outcomes of sepsis in human patients.

Hypothesis: Explore the correlation of RPR with sepsis in neonatal foals and evaluate RPR predictive and prognostic value.

Aclarubicin stimulates RNA polymerase II elongation at closely spaced divergent promoters.

Anthracyclines are a class of widely prescribed anti-cancer drugs that disrupt chromatin by intercalating into DNA and enhancing nucleosome turnover. To understand the molecular consequences of anthracycline-mediated chromatin disruption, we utilized CUT&Tag to profile RNA polymerase II during anthracycline treatment in cells. We observed that treatment with the anthracycline aclarubicin leads to elevated levels of elongating RNA polymerase II and changes in chromatin accessibility.

Seeking Racial Equity in Hematology and Oncology: a Fellow-Led Educational Series to Promote Reflection and Action.

The USA is experiencing a reckoning with racial injustice and graduate medical education programs are seeking ways to address this important topic in training. Fellows in hematology/oncology at the University of North Carolina recognized this important gap and adapted a curriculum for medical residents on racial equity to a subspecialty audience. Aims were (1) to improve knowledge and awareness about implicit bias and systemic racism and (2) introduce methods to address racial inequities.

Differential condensation of sister chromatids acts with Cdc6 to ensure asynchronous S-phase entry in Drosophila male germline stem cell lineage.

During Drosophila melanogaster male germline stem cell (GSC) asymmetric division, preexisting old versus newly synthesized histones H3 and H4 are asymmetrically inherited. However, the biological outcomes of this phenomenon have remained unclear. Here, we tracked old and new histones throughout the GSC cell cycle through the use of high spatial and temporal resolution microscopy.

A pairwise distance distribution correction (DDC) algorithm to eliminate blinking-caused artifacts in SMLM.

Single-molecule localization microscopy (SMLM) relies on the blinking behavior of a fluorophore, which is the stochastic switching between fluorescent and dark states. Blinking creates multiple localizations belonging to the same fluorophore, confounding quantitative analyses and interpretations. Here we present a method, termed distance distribution correction (DDC), to eliminate blinking-caused repeat localizations without any additional calibrations.

Pruriception and neuronal coding in nociceptor subtypes in human and nonhuman primates.

In humans, intradermal administration of β-alanine (ALA) and bovine adrenal medulla peptide 8-22 (BAM8-22) evokes the sensation of itch. Currently, it is unknown which human dorsal root ganglion (DRG) neurons express the receptors of these pruritogens, MRGPRD and MRGPRX1, respectively, and which cutaneous afferents these pruritogens activate in primate. In situ hybridization studies revealed that MRGPRD and MRGPRX1 are co-expressed in a subpopulation of TRPV1+ human DRG neurons.

Searching and Intertwining: Climbing Plants and GrowBots.

Applications in remote inspection and medicine have motivated the recent development of innovative thin, flexible-backboned robots. However, such robots often experience difficulties in maintaining their intended posture under gravitational and other external loadings. Thin-stemmed climbing plants face many of the same problems.

Retrospective Analyses Associate Hemostasis Activation Biomarkers With Poor Outcomes in Patients With COVID-19.

Objectives: Patients with coronavirus disease 2019 (COVID-19) have thromboembolic complications. Assessment of coagulation and other markers could be useful to understand their coagulopathy.

Methods: We performed a retrospective study of inflammatory and coagulation parameters, including prothrombin fragment 1.

A retrospective analysis of clinical use of alirocumab in lipoprotein apheresis patients.

Background: The previously published ODYSSEY ESCAPE trial demonstrated a significant reduction in the use of lipoprotein apheresis for heterozygous familial hypercholesterolemia (HeFH) patients when placed on alirocumab 150 mg every 2 weeks. In patients with HeFH who have consistently elevated levels of low-density lipoprotein cholesterol (LDL-C) despite maximally tolerated statin therapy, current lipid guidelines recommend apheresis. Although apheresis reduces LDL-C levels by 50%-75%, it must be repeated, as frequently as every 1-2 weeks.

Identification of novel synaptonemal complex components in C. elegans.

The synaptonemal complex (SC) is a tripartite protein scaffold that forms between homologous chromosomes during meiosis. Although the SC is essential for stable homologue pairing and crossover recombination in diverse eukaryotes, it is unknown how individual components assemble into the highly conserved SC structure. Here we report the biochemical identification of two new SC components, SYP-5 and SYP-6, in Caenorhabditis elegans.

Superresolution imaging of chromatin fibers to visualize epigenetic information on replicative DNA.

During DNA replication, the genetic information of a cell is copied. Subsequently, identical genetic information is segregated reliably to the two daughter cells through cell division. Meanwhile, DNA replication is intrinsically linked to the process of chromatin duplication, which is required for regulating gene expression and establishing cell identities.

Asymmetric Histone Inheritance in Asymmetrically Dividing Stem Cells.

Epigenetic mechanisms play essential roles in determining distinct cell fates during the development of multicellular organisms. Histone proteins represent crucial epigenetic components that help specify cell identities. Previous work has demonstrated that during the asymmetric cell division of Drosophila male germline stem cells (GSCs), histones H3 and H4 are asymmetrically inherited, such that pre-existing (old) histones are segregated towards the self-renewing GSC whereas newly synthesized (new) histones are enriched towards the differentiating daughter cell.

Financial Impact of Universal Precepting in Family Medicine Residency Clinics.

Background And Objectives: Precepting methods have significant impact on the financial viability of family medicine residency programs. Following an adverse event, four University of Minnesota Family Medicine residency clinics moved from using Medicare's Primary Care Exception (PCE) and licensure precepting (LP) to a "universal precepting" method in which preceptors see every patient face to face. Variation in the implementation of universal precepting created a natural experiment of its financial impact.

Investigating the Deoxyribonuclease Activity of CRM197 with Site-Directed Mutagenesis.

The protein cross-reactive material 197 (CRM197) is known to catalyze the hydrolytic cleavage of DNA (DNase activity). A suspected metal-binding site (S109, T111, and E112) and suspected DNA-binding motif (T89, K90, and V91) were predicted within the CRM197 protein X-ray crystal structure (4AE0) using METSITE and DNABindProt, respectively. Between these two predicted sites is a groove (K103, E116, T120, E122, F123, and R126) that may assist in DNase activity.