Association of ESR1 Germline Variants with TP53 Somatic Variants in Breast Tumors in a Genome-wide Study.

Unlabelled: In breast tumors, somatic mutation frequencies in TP53 and PIK3CA vary by tumor subtype and ancestry. Emerging data suggest tumor mutation status is associated with germline variants and genetic ancestry. We aimed to identify germline variants that are associated with somatic TP53 or PIK3CA mutation status in breast tumors.

Imbalance in Glucose Metabolism Regulates the Transition of Microglia from Homeostasis to Disease-Associated Microglia Stage 1.

Microglia undergo two-stage activation in neurodegenerative diseases, known as disease-associated microglia (DAM). TREM2 mediates the DAM2 stage transition, but what regulates the first DAM1 stage transition is unknown. We report that glucose dyshomeostasis inhibits DAM1 activation and PKM2 plays a role.

Transcriptional profiling of human cartilage endplate cells identifies novel genes and cell clusters underlying degenerated and non-degenerated phenotypes.

Background: Low back pain is a leading cause of disability worldwide and is frequently attributed to intervertebral disc (IVD) degeneration. Though the contributions of the adjacent cartilage endplates (CEP) to IVD degeneration are well documented, the phenotype and functions of the resident CEP cells are critically understudied. To better characterize CEP cell phenotype and possible mechanisms of CEP degeneration, bulk and single-cell RNA sequencing of non-degenerated and degenerated CEP cells were performed.

Association of germline variants with somatic variants in breast tumors in a genome-wide study.

Background: In breast tumors, somatic mutation frequencies in and vary by tumor subtype and ancestry. HER2 positive and triple negative breast cancers (TNBC) have a higher frequency of somatic mutations than other subtypes. mutations are more frequently observed in hormone receptor positive tumors.

Neutralization escape of Omicron XBB, BR.2, and BA.2.3.20 subvariants.

New Omicron subvariants continue to emerge throughout the world. In particular, the XBB subvariant, which is a recombinant virus between BA.2.

Enhanced evasion of neutralizing antibody response by Omicron XBB.1.5, CH.1.1, and CA.3.1 variants.

Omicron subvariants continuingly challenge current vaccination strategies. Here, we demonstrate nearly complete escape of the XBB.1.

Extraordinary Evasion of Neutralizing Antibody Response by Omicron XBB.1.5, CH.1.1 and CA.3.1 Variants.

Newly emerging Omicron subvariants continue to emerge around the world, presenting potential challenges to current vaccination strategies. This study investigates the extent of neutralizing antibody escape by new subvariants XBB.1.

Enhanced neutralization resistance of SARS-CoV-2 Omicron subvariants BQ.1, BQ.1.1, BA.4.6, BF.7, and BA.2.75.2.

The continued evolution of SARS-CoV-2 has led to the emergence of several new Omicron subvariants, including BQ.1, BQ.1.

Distinct Neutralizing Antibody Escape of SARS-CoV-2 Omicron Subvariants BQ.1, BQ.1.1, BA.4.6, BF.7 and BA.2.75.2.

Continued evolution of SARS-CoV-2 has led to the emergence of several new Omicron subvariants, including BQ.1, BQ. 1.

Targeting ETosis by miR-155 inhibition mitigates mixed granulocytic asthmatic lung inflammation.

Asthma is phenotypically heterogeneous with several distinctive pathological mechanistic pathways. Previous studies indicate that neutrophilic asthma has a poor response to standard asthma treatments comprising inhaled corticosteroids. Therefore, it is important to identify critical factors that contribute to increased numbers of neutrophils in asthma patients whose symptoms are poorly controlled by conventional therapy.

COVID-19 Booster Uptake among First Responders and Their Household Members May Be Lower than Anticipated.

(1) Background: COVID-19 vaccination status varies widely among law enforcement and emergency medical services professionals. Though at high risk of exposure, these first responders have demonstrated significant vaccine hesitancy, with only 70% reportedly vaccinated. We sought to understand whether similar vaccine hesitancy exists for first responders and their household contacts around COVID-19 boosters.

Differences in somatic TP53 mutation type in breast tumors by race and receptor status.

Purpose: Somatic driver mutations in TP53 are associated with triple-negative breast cancer (TNBC) and poorer outcomes. Breast cancers in women of African ancestry (AA) are more likely to be TNBC and have somatic TP53 mutations than cancers in non-Hispanic White (NHW) women. Missense driver mutations in TP53 have varied functional impact including loss-of-function (LOF) or gain-of-function (GOF) activity, and dominant negative (DNE) effects.

The Utility of Point-of-Care Biomarkers to Detect Cardiotoxicity During Anthracycline Chemotherapy: A Feasibility Study.

Background: Anthracycline chemotherapy is associated with an increased risk of developing heart failure (HF). The current standard for detecting HF or cardiotoxicity during chemotherapy involves episodic cardiac imaging typically at prescribed intervals and there are limited studies examining techniques beyond measuring left ventricular (LV) function. This study explores whether cardiac biomarkers troponin I (TnI) and B-type natriuretic peptide (BNP) could be part of a screening strategy for early detection of the development of cardiotoxicity in patients undergoing anthracycline chemotherapy.

Cardiotoxicity due to Chemotherapy: the Role of Biomarkers.

An ever-increasing array of chemotherapeutic agents is being used in the treatment of solid organ or hematologic malignancies. The success of many of these agents has led to an increasing survival of patients with cancer. However, many of these agents, particularly anthracyclines and trastuzumab, are associated with the development of cardiotoxicity.

Creatine protects against mitochondrial dysfunction associated with HIV-1 Tat-induced neuronal injury.

HIV-1 infected individuals live longer but experience a prevalence rate of over 50% for HIV-1 associated neurocognitive disorders (HAND) for which no effective treatment is available. Viral and cellular factors secreted by HIV-1 infected cells lead to neuronal injury and HIV-1 Tat continues to be implicated in the pathogenesis of HAND. Here we tested the hypothesis that creatine protected against HIV-1 Tat-induced neuronal injury by preventing mitochondrial bioenergetic crisis and/or redox catastrophe.

Chronic rhinosinusitis osteoblasts differ in cellular properties from normal bone.

Background: Osteitis, characterized by bony thickening and remodeling, is often considered a hallmark of recalcitrant rhinosinusitis. However, there is limited literature examining the bone in chronic rhinosinusitis (CRS) pathology. In this study we cultured osteoblasts from bone harvested during sinus surgery as well as from nondiseased controls to compare their cellular properties.

Adult neuroblastoma complicated by increased intracranial pressure: a case report and review of the literature.

Neuroblastoma is the third most commonly occurring malignancy of the pediatric population, although it is extremely rare in the adult population. In adults, neuroblastoma is often metastatic and portends an extremely poor overall survival. Our case report documents metastatic neuroblastoma occurring in a healthy 29-year-old woman whose course was complicated by an unusual presentation of elevated intracranial pressures.

Immune surveillance and lymphoid malignancy in immunocompromised host.

Immune surveillance is a dynamic process that involves an intact immune system to identify and protect the host against tumor development. The increased understanding of the genetics, infections and hematological malignancies in congenital immune deficiency states supports the concept that impaired T cells and Natural-killer/T cells leads to B-cell lymphoma. Furthermore, severe combined immunodeficient mice are prone to spontaneous tumor development and therefore serve as experimental models.

Advances and application of radioimmunotherapy in non-Hodgkin lymphoma.

The activity of radio-immuno conjugate in Non-Hodgkin Lymphoma (NHL) has resulted in FDA approval of two antibodies, Y(90) Ibritumomab tiuxetan and I(131) tositumomab. Both these agents target CD20, a receptor widely expressed in B-Cell NHL. These immunoconjugates deliver their radioactive payload to the malignant clone in the bone marrow and lymph node.

The role of smoking in Crohn's disease as defined by clinical variables.

The development of Crohn's disease (CD) is related to an interaction of genetic and environmental factors, with tobacco smoking being one of the most commonly studied environmental factors. In 1998, the Vienna classification was created to define CD by using three accepted clinical variables: age at diagnosis, disease behavior, and disease location. In this qualitative systematic review, articles examining the relationship between smoking and CD, using variables outlined in the Vienna classification, were identified utilizing multiple health databases.

Dose distribution to spinal structures from intrathecally administered yttrium-90.

Previous treatment of cerebrospinal fluid (CSF) malignancies by intrathecal administration of (131)I-radiolabelled monoclonal antibodies has led to the assumption that more healthy tissue will be spared when a pure beta-emitter such as (90)Y replaces (131)I. The purpose of this study is to compare and quantitatively evaluate the dose distribution from (90)Y to the CSF space and its surrounding spinal structures to (131)I. A 3D digital phantom of a section of the T-spine was constructed from the visible human project series of images which included the spinal cord, central canal, subarachnoid space, pia mater, arachnoid, dura mater, vertebral bone marrow and intervertebral disc.

Purine level regulation during energy depletion associated with graded excitatory stimulation in brain.

Objectives: The formation and release of adenosine following graded excitatory stimulation of the brain may serve important physiological functions such as sleep regulation, as well as an early resistance mechanism against excitotoxicity. However, adenosine at high levels may reflect merely the results of obstructed energy metabolism.

Methods: We examined the extent to which levels of adenosine and adenylate energy charge are affected in vivo by graded excitatory stimulations of brain using unilateral intrastriatal injections of glutamatergic agents and head-focused high energy microwaving for accurate and precise measures of purines.