LIN-67 functionally interacts with heterochronic miRNAs and regulates developmental timing in .

Temporal regulation of gene expression is required for developmental transitions, including differentiation, proliferation, and morphogenesis. In the nematode , heterochronic microRNAs (miRNAs) regulate the temporal expression of genes that promote animal development. The heterochronic miRNAs lin-4 and let-7 are required during different stages of larval development and are associated with the miRNA-specific Argonaute ALG-1.

Sotatercept: A New Era in Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) is a progressive disease characterized by proliferative remodeling and obliterative narrowing of the pulmonary vasculature. While outcomes have improved with existing treatments targeting 3 main pathways, there remains a critical need for novel therapies that address different and novel mechanisms of PAH. Sotatercept, recently Food and Drug Administration (FDA) approved, is a groundbreaking fusion protein that binds to activin and growth differentiation factors, rebalancing antiproliferative and pro-proliferative signals to reverse remodeling in both the pulmonary vasculature and the right ventricle.

The landscape of primary mismatch repair deficient gliomas in children, adolescents, and young adults: a multi-cohort study.

Background: Gliomas are a major cause of cancer-related death among children, adolescents, and young adults (age 0-40 years). Primary mismatch repair deficiency (MMRD) is a pan-cancer mechanism with unique biology and therapeutic opportunities. We aimed to determine the extent and impact of primary MMRD in gliomas among children, adolescents, and young adults.

Effects of Socioeconomic Status and Healthcare Resource Availability on Survival in Older (≥66 years) Non-Hispanic Black Patients Versus Non-Hispanic White Patients With Multiple Myeloma.

Background: Several factors contribute to the known disparities in overall survival (OS) between non-Hispanic Black (NHB) patients and non-Hispanic White (NHW) patients with multiple myeloma (MM).

Patients And Methods: To explore whether socioeconomic status (SES) and healthcare resource (HCR) availability impacts OS, this retrospective study used linked Surveillance, Epidemiology, and End Results (SEER)-Medicare claims and Area Health Resource Files to identify NHB and NHW patients aged ≥66 years with MM (newly diagnosed 6/1/2013-12/31/2017). Continuous Medicare A and B enrollment until 12/31/2019 or preceding death was required.

Impact of syndemic heavy drinking, smoking, and depression on mortality among MSM with and without HIV: A longitudinal study.

Background: Heavy drinking, smoking, and depression are common among men who have sex with men (MSM). The association of co-occurring longitudinal patterns of these conditions and mortality among MSM were tested, applying a syndemic framework - the interaction of two or more conditions that contribute to poor health outcomes.

Methods: Longitudinal data from 1999 to 2018 from the Multicenter AIDS Cohort Study of 3046 MSM were analyzed.

Creating a plasma coordination center to support COVID-19 outpatient trials across a national network of hospital blood banks.

Introduction: In response to the COVID-19 pandemic, we rapidly implemented a plasma coordination center, within two months, to support transfusion for two outpatient randomized controlled trials. The center design was based on an investigational drug services model and a Food and Drug Administration-compliant database to manage blood product inventory and trial safety.

Methods: A core investigational team adapted a cloud-based platform to randomize patient assignments and track inventory distribution of control plasma and high-titer COVID-19 convalescent plasma of different blood groups from 29 donor collection centers directly to blood banks serving 26 transfusion sites.

Fertilizer management approaches influence nutrient leaching from residential landscapes.

Residential lawn management often includes fertilizer application to encourage healthy plant growth and support the aesthetic preferences of homeowners and communities. These inputs may negatively impact the environment by increasing nutrient export to aquatic ecosystems via surface runoff or leaching through soil into groundwater. Fertilizer management and nutrient export are of particular concern in karst areas like North-Central Florida, where the underlying karst geology leads to rapid, direct connections between surface and groundwater ecosystems.

Clustering of variants into functional classes correlates with cancer risk and identifies different phenotypes of Li-Fraumeni syndrome.

Li-Fraumeni syndrome (LFS) is a heterogeneous predisposition to an individually variable spectrum of cancers caused by pathogenic germline variants. We used a clustering method to assign TP53 missense variants to classes based on their functional activities in experimental assays assessing biological p53 functions. Correlations with LFS phenotypes were analyzed using the public germline mutation database and validated in three LFS clinical cohorts.

Opportunities and challenges of single-cell and spatially resolved genomics methods for neuroscience discovery.

Over the past decade, single-cell genomics technologies have allowed scalable profiling of cell-type-specific features, which has substantially increased our ability to study cellular diversity and transcriptional programs in heterogeneous tissues. Yet our understanding of mechanisms of gene regulation or the rules that govern interactions between cell types is still limited. The advent of new computational pipelines and technologies, such as single-cell epigenomics and spatially resolved transcriptomics, has created opportunities to explore two new axes of biological variation: cell-intrinsic regulation of cell states and expression programs and interactions between cells.

Transmembrane prostatic acid phosphatase: a therapeutic target in advanced prostate cancer.

Prostate cancer (PCa) is the most common cancer and second leading cause of cancer death in American men. Most patients with metastatic disease respond initially to androgen deprivation therapy (ADT), but almost inevitably progress to castration resistant prostate cancer (CRPC). Identification of markers and drivers of mCRPC that (a) represent a progenitor-type cancer cell population (b) persist in castration resistant disease (c) are actionable targets expressed on the cell surface, and (d) are induced by hypoxia, is required to facilitate the development of novel targeted therapies.

From Processed Foods to Ultraprocessed Foods: Evolution of an Industry Model and Impact on Dietary Quality, Health, and Society.

The impact of food technology and product development on the nutritional quality of foods is discussed in the context of food classification schemes, clinical research, and sociocultural studies. Food processing operations are analyzed in terms of their beneficial and detrimental consequences for the nutritional value of foods and ingredients. Several classification schemes are discussed, including dietary guidelines, nutrition information panels, and nutritional scores.

Using Less Processed Food to Mimic a Standard American Diet Does Not Improve Nutrient Value and May Result in a Shorter Shelf Life at a Higher Financial Cost.

Background: The "clean eating" trend suggests that consuming fewer processed foods is important for healthy diets. Yet, a diet of mostly ultra-processed foods (UPFs) can meet recommendations from the Dietary Guidelines for Americans. Whether a diet comprised mostly of simple ingredient foods can provide a low-quality diet remains unexplored.

A novel digital health approach to improving global pediatric sepsis care in Bangladesh using wearable technology and machine learning.

Sepsis is the leading cause of child death globally with low- and middle-income countries (LMICs) bearing a disproportionate burden of pediatric sepsis deaths. Limited diagnostic and critical care capacity and health worker shortages contribute to delayed recognition of advanced sepsis (severe sepsis, septic shock, and/or multiple organ dysfunction) in LMICs. The aims of this study were to 1) assess the feasibility of a wearable device for physiologic monitoring of septic children in a LMIC setting and 2) develop machine learning models that utilize readily available wearable and clinical data to predict advanced sepsis in children.

Combination treatment with histone deacetylase and carbonic anhydrase 9 inhibitors shows therapeutic potential in experimental diffuse intrinsic pontine glioma.

Diffuse intrinsic pontine glioma (DIPG) remains a significant therapeutic challenge due to the lack of effective and safe treatment options. This study explores the potential of combining histone deacetylase (HDAC) and carbonic anhydrase 9 (CA9) inhibitors in treating DIPG. Analysis of RNA sequencing data and tumor tissue from patient samples for the expression of the carbonic anhydrase family and hypoxia signaling pathway activity revealed clinical relevance for targeting CA9 in DIPG.