The spatial structure of the tumor immune microenvironment can explain and predict patient response in high-grade serous carcinoma.

Despite ovarian cancer being the deadliest gynecological malignancy, there has been little change to therapeutic options and mortality rates over the last three decades. Recent studies indicate that the composition of the tumor immune microenvironment (TIME) influences patient outcomes but are limited by a lack of spatial understanding. We performed multiplexed ion beam imaging (MIBI) on 83 human high-grade serous carcinoma tumors - one of the largest protein-based, spatially-intact, single-cell resolution tumor datasets assembled - and used statistical and machine learning approaches to connect features of the TIME spatial organization to patient outcomes.

Peer feedback: A tool to improve PA, NP, and physician collaboration and clinical practice.

The increasing use of physician associates/assistants (PAs) and NPs on clinical teams creates an opportunity for colleagues to provide feedback that can drive growth and improvement in PA and NP clinical skills. Through a needs assessment, month-long pilot, and buy-in from our academic hospital medicine group, we initiated a peer feedback platform that sought to highlight individual faculty strengths, facilitate thoughtful and constructive feedback, and create effective collaboration among colleagues. Three months after implementation, results indicated that the platform provided important information on clinical skills and identified areas for growth and opportunities for additional training.

Canine diabetes mellitus demonstrates multiple markers of chronic inflammation including Th40 cell increases and elevated systemic-immune inflammation index, consistent with autoimmune dysregulation.

Introduction: Canine diabetes mellitus (CDM) is a relatively common endocrine disease in dogs. Many CDM clinical features resemble human type 1 diabetes mellitus (T1DM), but lack of autoimmune biomarkers makes calling the disease autoimmune controversial. Autoimmune biomarkers linking CDM and T1DM would create an alternative model for drug development impacting both human and canine disease.

How One Health Instrumentalizes Nonhuman Animals.

This article interrogates anthropocentrism and nonhuman animal instrumentalization in One Health (OH). It argues that OH's approach to human health and zoonosis focuses too narrowly on furthering certain human interests at the expense of nonhuman animals, which is not sustainable, just, or compassionate. This article also offers an alternative vision for protecting and promoting health for all over the long term that includes the human right to self-determination and the nonhuman animal right to not be exploited or abused.

The effects of early time restricted eating plus daily caloric restriction compared to daily caloric restriction alone on continuous glucose levels.

Background: The median eating duration in the U.S. is 14.

CASC4/GOLM2 drives high grade serous carcinoma anoikis resistance through the recycling of EGFR.

Ovarian cancer is the deadliest gynecological malignancy, and accounts for over 150,000 deaths per year worldwide. The high grade serous ovarian carcinoma (HGSC) subtype accounts for almost 70% of ovarian cancers and is the deadliest. HGSC originates in the fimbria of the fallopian tube and disseminates through the peritoneal cavity.

The Need for Responsive Workforce Development During the Pandemic and Beyond: A Case Study of the Regional Public Health Training Centers.

Context: The COVID-19 pandemic underscored the importance of a strong public health infrastructure for protecting and supporting the health of communities. This includes ensuring an adaptive workforce capable of leading through rapidly changing circumstances, communicating effectively, and applying systems thinking to leverage cross-sector partnerships that help promote health equity. The 10 Regional Public Health Training Centers (PHTCs) advance the capacity of the current and future public health workforce through skill development and technical assistance in these and other strategic areas.

Transcription dosage compensation does not occur in Down syndrome.

Background: The increase in DNA copy number in Down syndrome (DS; caused by trisomy 21) has led to the DNA dosage hypothesis, which posits that the level of gene expression is proportional to the gene's DNA copy number. Yet many reports have suggested that a proportion of chromosome 21 genes are dosage compensated back towards typical expression levels (1.0×).

Secondary hypogammaglobulinemia in patients with multiple sclerosis on anti-CD20 therapy: Pathogenesis, risk of infection, and disease management.

Hypogammaglobulinemia is characterized by reduced serum immunoglobulin levels. Secondary hypogammaglobulinemia is of considerable interest to the practicing physician because it is a potential complication of some medications and may predispose patients to serious infections. Patients with multiple sclerosis (MS) treated with B-cell-depleting anti-CD20 therapies are particularly at risk of developing hypogammaglobulinemia.

Rab35 is required for embryonic development and kidney and ureter homeostasis through regulation of epithelial cell junctions.

Background: Rab35 is a member of a GTPase family of endocytic trafficking proteins. Studies in cell lines have indicated that Rab35 participates in cell adhesion, polarity, cytokinesis, and primary cilia length and composition. Additionally, sea urchin Rab35 regulates actin organization and is required for gastrulation.

A Life-Affirming Palliative Care Model for Severe and Enduring Anorexia Nervosa.

Some individuals with severe and enduring anorexia nervosa experience dramatically degraded quality of life in the face of refractory illness and compulsory treatment. We propose a palliative care (PC) model for this group of patients that aims to support their unique goals of care, improve social-professional function, reduce physical suffering, and honor the whole person. Far from representing a pre-hospice model, a PC model for those with severe and enduring anorexia nervosa instead provides an alternative to current practices in hopes of meaningfully improving quality of life and outcomes.

Native top-down proteomics reveals EGFR-ERα signaling crosstalk in breast cancer cells dissociates NUTF2 dimers to modulate ERα signaling and cell growth.

Oligomerization of proteins and their modified forms (proteoforms) produces functional protein complexes . Complexoforms are complexes that consist of the same set of proteins with different proteoforms . The ability to characterize these assemblies within cells is critical to understanding the molecular mechanisms involved in disease and to designing effective drugs.

The association of allostasis with alcohol use: A case-control study in males with and without alcohol use disorder.

Background: Allostatic load (AL) is associated with a heightened predisposition to disease due to prolonged activation of biological stress-response systems. Alcohol use disorder (AUD) is known to activate these systems. The primary aim of the current study was to examine the relationship between AL and AUD.

Novel chromobox 2 inhibitory peptide decreases tumor progression.

Background: The Polycomb Repressor Complex 1 (PRC1) is an epigenetic regulator of differentiation and development, consisting of multiple subunits including RING1, BMI1, and Chromobox. The composition of PRC1 dictates its function and aberrant expression of specific subunits contributes to several diseases including cancer. Specifically, the reader protein Chromobox2 (CBX2) recognizes the repressive modifications including histone H3 lysine 27 tri-methylation (H3K27me3) and H3 lysine 9 dimethylation (H3K9me2).

Hospice Nurse Ethics and Institutional Policies Toward Medical Aid in Dying.

A significant number of hospices in U.S. jurisdictions where medical aid in dying is legal have implemented policies that require nurses to leave the room when a patient ingests aid-in-dying medication.

LPCAT1 levels in the placenta, the maternal plasma and the fetal plasma do not predict fetal lung responses to glucocorticoids in a sheep model of pregnancy.

Introduction: Lysophosphatidylcholine acyltransferase 1 (LPCAT1) is important for saturated phosphatidylcholine (Sat-PC) production in the lung. Sat-PC is a critical component of pulmonary surfactant, which maintains low alveolar surface tension, facilitating respiration. Previous studies have reported an association between maternal and fetal LPCAT1 levels and neonatal lung function.

Management Considerations for Patients With Primary Refractory and Early Relapsed Diffuse Large B-Cell Lymphoma.

Most patients with diffuse large B-cell lymphoma (DLBCL) will be cured with up-front chemoimmunotherapy, but 30%-40% of patients will experience relapsed disease. Historically, salvage chemotherapy followed by autologous stem-cell transplant (ASCT) was the mainstay of treatment for these patients. However, research has demonstrated that patients with primary refractory or early relapsed (R/R; high-risk) DLBCL do not benefit from ASCT, prompting investigation into other options.

Cellular reprogramming of fibroblasts in heart regeneration.

Myocardial infarction causes the loss of cardiomyocytes and the formation of cardiac fibrosis due to the activation of cardiac fibroblasts, leading to cardiac dysfunction and heart failure. Unfortunately, current therapeutic interventions can only slow the disease progression. Furthermore, they cannot fully restore cardiac function, likely because the adult human heart lacks sufficient capacity to regenerate cardiomyocytes.

Cultural Competence and Humility.

The increasing diversification of the United States has led to more racially and ethnically discordant visits between health care providers and patients; this is especially true in dermatology due to the lack of diversity in the field. Diversifying the health care workforce has been shown to reduce health care disparities and is an ongoing goal of dermatology. Improving cultural competence and humility among physicians is an important part of addressing health care inequities.

Combinatory EHMT and PARP inhibition induces an interferon response and a CD8 T cell-dependent tumor regression in PARP inhibitor-resistant models.

Euchromatic histone lysine methyltransferases 1 and 2 (EHMT1/2), which catalyze demethylation of histone H3 lysine 9 (H3K9me2), contribute to tumorigenesis and therapy resistance through unknown mechanisms of action. In ovarian cancer, EHMT1/2 and H3K9me2 are directly linked to acquired resistance to poly-ADP-ribose polymerase (PARP) inhibitors and are correlated with poor clinical outcomes. Using a combination of experimental and bioinformatic analyses in several PARP inhibitor resistant ovarian cancer models, we demonstrate that combinatory inhibition of EHMT and PARP is effective in treating PARP inhibitor resistant ovarian cancers.

Encoding of 3D physical dimensions by face-selective cortical neurons.

Neurons throughout the primate inferior temporal (IT) cortex respond selectively to visual images of faces and other complex objects. The response magnitude of neurons to a given image often depends on the size at which the image is presented, usually on a flat display at a fixed distance. While such size sensitivity might simply reflect the angular subtense of retinal image stimulation in degrees, one unexplored possibility is that it tracks the real-world geometry of physical objects, such as their size and distance to the observer in centimeters.

Azithromycin to Prevent Sepsis or Death in Women Planning a Vaginal Birth.

Background: The use of azithromycin reduces maternal infection in women during unplanned cesarean delivery, but its effect on those with planned vaginal delivery is unknown. Data are needed on whether an intrapartum oral dose of azithromycin would reduce maternal and offspring sepsis or death.

Methods: In this multicountry, placebo-controlled, randomized trial, we assigned women who were in labor at 28 weeks' gestation or more and who were planning a vaginal delivery to receive a single 2-g oral dose of azithromycin or placebo.