Molecular Profiling Identifies CD49d and CD79b as Predictive Markers for Acquired Acalabrutinib Resistance in Patients With Chronic Lymphocytic Leukemia.

Contemporary studies of Bruton tyrosine kinase inhibitor (BTKi) resistance focus on mutations in the B-cell receptor (BCR) pathway, but alternative mechanisms of resistance remain undefined. Here, we sought to identify novel predictive markers of acquired resistance to acalabrutinib, a second-generation BTKi, in patients with chronic lymphocytic leukemia (CLL). Clinical samples from 41 patients with relapsed/refractory or treatment-naive CLL receiving acalabrutinib as part of a clinical trial (NCT02029443) were divided into two groups: those who continued to respond to treatment (NP, n = 23) and those who developed progressive disease on acalabrutinib therapy (PD, n = 18).

Optimal Timing for Safe Bivalving of Fiberglass Casts Is Before the Exothermic Peak.

Introduction: Cast saw injury is a notable source of medicolegal risk. Previous work with plaster casts demonstrated that cast saw injury was minimized by waiting 12 minutes before removal. In this study, we evaluate the safety parameters of fiberglass casting materials.

Genotype-immunophenotype relationships in -mutant AML clonal evolution uncovered by single cell multiomic analysis.

Acute myeloid leukemia (AML) is a multi-clonal disease, existing as a milieu of clones with unique but related genotypes as initiating clones acquire subsequent mutations. However, bulk sequencing cannot fully capture AML clonal architecture or the clonal evolution that occurs as patients undergo therapy. To interrogate clonal evolution, we performed simultaneous single cell molecular profiling and immunophenotyping on 43 samples from 32 -mutant AML patients at different stages of disease.

Improving risk stratification for 2022 European LeukemiaNet favorable-risk patients with acute myeloid leukemia.

Assignment of patients diagnosed with acute myeloid leukemia (AML) to the 2022 European LeukemiaNet (ELN) favorable genetic risk group has important clinical implications, as allogeneic stem cell transplantation in first complete remission (CR) is not advised due to a relatively good outcome of patients receiving chemotherapy alone and transplant-associated mortality. However, not all favorable genetic risk patients experience long-term relapse-free survival (RFS), making recognition of patients who would most likely be cured of high importance. We analyzed 297 patients aged <60 years with AML classified as 2022 ELN favorable genetic risk who achieved a CR and had RNA sequencing (RNA-seq) and gene mutation data from diagnostic samples available (Alliance trial A152010).

Genotype-phenotype correlations in 294 pediatric patients with osteogenesis imperfecta.

Osteogenesis imperfecta (OI) is an inherited disorder characterized by bone fragility with extraskeletal manifestations mostly due to and variants. Currently, 23 genes have been implicated in the pathogenesis of OI; however, literature on genotype-phenotype correlation and incidence of non-skeletal clinical features are limited. This study aims to identify genotype-phenotype correlations in patients with OI, allowing clinicians to better inform families of prognosis, optimize patient care, and facilitate evidence-based clinical decision-making.

Multiomic profiling identifies predictors of survival in African American patients with acute myeloid leukemia.

Genomic profiles and prognostic biomarkers in patients with acute myeloid leukemia (AML) from ancestry-diverse populations are underexplored. We analyzed the exomes and transcriptomes of 100 patients with AML with genomically confirmed African ancestry (Black; Alliance) and compared their somatic mutation frequencies with those of 323 self-reported white patients with AML, 55% of whom had genomically confirmed European ancestry (white; BeatAML). Here we find that 73% of 162 gene mutations recurrent in Black patients, including a hitherto unreported PHIP alteration detected in 7% of patients, were found in one white patient or not detected.

CD37 in acute myeloid leukemia: a novel surface target for drug delivery.

Acute myeloid leukemia (AML) is the most common and lethal leukemia in adults. AML consists of many genetic subtypes, which limits broad applicability of targeted therapy. We discovered that the hematopoiesis-restricted tetraspanin CD37 is expressed on the majority of primary AML blasts and thus may represent a common therapeutic target for AML regardless of subtype.

Mutation Clonal Hierarchy in Acute Myeloid Leukemia.

Mutations in protein tyrosine phosphatase non-receptor type 11 ( ) have been considered late acquired mutations in acute myeloid leukemia (AML) development. To interrogate the ontogeny of mutations, we utilized single-cell DNA sequencing and identified that mutations can occur as initiating events in some AML patients when accompanied by strong oncogenic drivers, commonly mutations. The co-driver role of mutations was confirmed in a novel murine model that exhibits an AML phenotype with early expansion of a diverse set of variably differentiated myeloid cells that engrafted into immunodeficient and immunocompetent mice.

Massively Parallel Computational Chemistry with the Super Instruction Architecture and ACES4.

The task of developing high-performing parallel software must be made easier and more cost-effective in order to fully exploit existing and emerging large-scale computer systems for the advancement of science. The Super Instruction Architecture (SIA) is a parallel programming platform geared toward applications that need to manage large amounts of data stored in potentially sparse multidimensional arrays during calculations. The SIA platform was originally designed for the quantum chemistry software package ACESIII.

LP-118 is a novel B-cell lymphoma 2 / extra-large inhibitor that demonstrates efficacy in models of venetoclax-resistant chronic lymphocytic leukemia.

Patients with chronic lymphocytic leukemia (CLL) respond well to initial treatment with the Bcell lymphoma 2 (BCL2) inhibitor venetoclax. Upon relapse, they often retain sensitivity to BCL2 targeting, but durability of response remains a concern. We hypothesize that targeting both BCL2 and B-cell lymphoma-extra large (BCLXL) will be a successful strategy to treat CLL, including for patients who relapse on venetoclax.

Linking norepinephrine production and performance to diet-induced low-grade, chronic inflammation in the intestine of broilers.

Maintenance of intestinal health is critical to successful poultry production and one of the goals of the poultry production industry. For decades the poultry industry has relied upon the inclusion of antibiotic growth promoters (AGP) to achieve this goal and improve growth performance. With the removal of AGPs, the emergence of chronic, low-level gut inflammation has come to the forefront of concern in the poultry industry with the diet being the primary source of inflammatory triggers.

What do child maltreatment reports to Child Protective Services tell us about the needs families and communities are experiencing?

Intake reports from child protective service (CPS) agencies are the foundation for subsequent decisions and services within the child welfare system. They provide valuable information for understanding children's needs, yet the unstructured way that information is captured makes the information ascertained in these reports difficult to summarize. Utilizing CPS intake reports from a mid-sized urban county in the southeastern United States (N = 2,724), our study had three aims: (1) develop a coding system to abstract information from narrative CPS intake reports, (2) examine the prevalence of maltreatment subtypes, and (3) compare prevalence of maltreatment subtypes by screen-in/screen-out decisions.

Nocturnal systolic blood pressure dipping among people living with HIV and people without HIV: a cross-sectional study in Rural Uganda.

Background: In this study, we investigated sleep quality, depression and stress symptoms as hypothesized factors affecting the association between HIV status and nocturnal blood pressure dipping status in rural Uganda.

Methods: Individuals living with HIV (PLHIV) and people without HIV (PwoHIV) underwent 24-hour ambulatory blood pressure monitoring (ABPM) and classified as extreme dippers, dippers and non-dippers based on a percentage nocturnal drop in mean systolic and diastolic blood pressure. Ordinal logistic regression models were used to assess the effect of different exposure variables (HIV status, sleep quality and other covariates) on the outcome (dipping status).

NOD2 activation enhances macrophage Fcγ receptor function and may increase the efficacy of antibody therapy.

Introduction: Therapeutic antibodies have become a major strategy to treat oncologic diseases. For chronic lymphocytic leukemia, antibodies against CD20 are used to target and elicit cytotoxic responses against malignant B cells. However, efficacy is often compromised due to a suppressive microenvironment that interferes with cellular immune responses.

Cardiovascular Dynamics in HIV: The Influence of Adrenal Function and Nutritional Status.

This interdisciplinary review explores the intricate nexus between HIV infection, nutrition, adrenal gland function, and cardiovascular health, highlighting a critical aspect of HIV management often overlooked in current literature. With the advent of antiretroviral therapy, the life expectancy of people living with HIV has dramatically improved, transforming HIV into a manageable chronic condition. However, this success brings forth new challenges, notably an increased risk of cardiovascular diseases among people living with HIV.

Mutational profile in previously treated patients with chronic lymphocytic leukemia progression on acalabrutinib or ibrutinib.

Chronic lymphocytic leukemia (CLL) progression during Bruton tyrosine kinase (BTK) inhibitor treatment is typically characterized by emergent B-cell receptor pathway mutations. Using peripheral blood samples from patients with relapsed/refractory CLL in ELEVATE-RR (NCT02477696; median 2 prior therapies), we report clonal evolution data for patients progressing on acalabrutinib or ibrutinib (median follow-up, 41 months). Paired (baseline and progression) samples were available for 47 (excluding 1 Richter) acalabrutinib-treated and 30 (excluding 6 Richter) ibrutinib-treated patients.

The Clinical Course of a Severe Case of Malignant Catatonia.

Catatonia is a psychomotor syndrome predominantly associated with mental illness disorders, most commonly bipolar disorder and schizophrenia. Catatonia is classified as malignant when, in addition to catatonic symptoms, dysautonomia is present. Autonomic abnormalities can include changes in temperature, labile blood pressure, and changes in heart and respiratory rates.

Intractable Aspiration Treated With Laryngectomy After SLAD-R Surgery: A Case Report.

A variety of surgical treatment options exist for adductor spasmodic dysphonia (ADSD) with selective adductor recurrent laryngeal nerve denervation and reinnervation (SLAD-R) being one of the more popular. We present a case of bilateral vocal fold paralysis (BVFP) for SLAD-R resulting in the need for total laryngectomy. We suggest BVFP is more common than reported and that we all must insure optimal long term follow up of our surgical patients.