BRAT1 - a new therapeutic target for glioblastoma.

Glioblastoma (GBM), the most malignant primary brain tumor in adults, has poor prognosis irrespective of therapeutic advances due to its radio-resistance and infiltrative growth into brain tissue. The present study assessed functions and putative druggability of BRCA1-associated ATM activator 1 (BRAT1) as a crucial factor driving key aspects of GBM, including enhanced DNA damage response and tumor migration. By a stable depletion of BRAT1 in GBM and glioma stem-like (GSC) cell lines, we observed a delay in DNA double-strand break repair and increased sensitivity to radiation treatment, corroborated by in vitro and in vivo studies demonstrating impaired tumor growth and invasion.

Implementation of a Faith Community Nursing Transition of Care Program in the USA: A Propensity Score Matching Analysis.

Faith community nursing (FCN) is a specialty nursing practice that integrates spiritual and religious practices into patient care. This study aimed to quantitatively assess the impact of the standardized FCN transition of care (TOC) program on the rate of hospital readmission and length of stay (LOS) through propensity score matching and difference-in-differences methods. Compared with those in the non-FCN group (n = 409), patients in the FCN group (n = 66) had a reduced likelihood of hospital readmission at 30, 90, and 180 days after discharge (by 8.

A comparative evaluation of CRISPR-Cas9 allele editing systems in : challenging research in a challenging bug.

is an emergent fungal pathogen of significant interest for molecular research because of its unique nosocomial persistence, high stress tolerance and common multidrug resistance. To investigate the molecular mechanisms of these or other phenotypes, a handful of CRISPR-Cas9 based allele editing tools have been optimized for . Nonetheless, allele editing in this species remains a significant challenge and different systems have different advantages and disadvantages.

Impacts of Ethical Dilemmas and Moral Distress in Pediatric Hematology Oncology Nurses.

Purpose: To assess the level of moral distress (MD) and perceptions of ethical climate among pediatric hematology/oncology (PHO) nurses and to identify bioethics topics where increased education was desired.

Methods: In this cross-sectional study, we administered the 26-item Swedish Moral Distress Scale-Revised (sMDS-R), specifically revised and validated for pediatric oncology, in conjunction with the Clinical Ethics Needs Assessment Survey (CENAS). Electronic surveys were sent to inpatient and outpatient PHO nurses.

Interplay of canonical and LIMK mediated non-canonical BMP signaling is essential for regulating differential thickness and invagination during chick forebrain roof plate morphogenesis.

Telencephalic hemisphere formation is a complex and precisely timed process, which begins in the chick forebrain with an invagination in the middle of the roof plate. However, the factor(s) that determine the position/site of invagination in the roof plate remain to be elucidated. In this study, we have demonstrated that as development proceeds, a region of lower thickness appears in the middle of the roof plate, which marks the position where the invagination begins.

Response to induction chemotherapy modifies the effect of conventional prognostic factors in high-risk neuroblastoma: A report from the Children's Oncology Group.

Background: Response to induction chemotherapy has been shown to predict outcome in patients with high-risk neuroblastoma (HR-NB), with those achieving a complete response (CR) having superior outcomes.

Methods: We evaluated whether conventional prognostic factors remain prognostic in subsets of patients defined by response to induction. 1244 Patients from four COG high-risk trials were included.

Head and Neck Paraganglioma in Pacak-Zhuang Syndrome.

Head and neck paragangliomas (HNPGLs) are typically slow-growing, hormonally inactive tumors of parasympathetic paraganglia. Inactivation of prolyl-hydroxylase domain-containing 2 protein causing indirect gain-of-function of hypoxia-inducible factor-2α (HIF-2α), encoded by EPAS1, was recently shown to cause carotid body hyperplasia. We previously described a syndrome with multiple sympathetic paragangliomas caused by direct gain-of-function variants in EPAS1 (Pacak-Zhuang syndrome, PZS) and developed a corresponding mouse model.

Analyzing Geospatial and Socioeconomic Disparities in Breast Cancer Screening Among Populations in the United States: Machine Learning Approach.

Background: Breast cancer screening plays a pivotal role in early detection and subsequent effective management of the disease, impacting patient outcomes and survival rates.

Objective: This study aims to assess breast cancer screening rates nationwide in the United States and investigate the impact of social determinants of health on these screening rates.

Methods: Data on mammography screening at the census tract level for 2018 and 2020 were collected from the Behavioral Risk Factor Surveillance System.

NCCN Guidelines® Insights: Lung Cancer Screening, Version 1.2025.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Lung Cancer Screening provide criteria for selecting individuals for screening and offer recommendations for evaluating and managing lung nodules detected during initial and subsequent annual screening. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines for Lung Cancer Screening.

Your Blood is Out for Delivery: Considerations of Shipping Time and Temperature on Degradation of RNA from Stabilized Whole Blood.

Remote research studies are an invaluable tool for reaching populations with limited access to large medical centers or universities. To expand the remote study toolkit, we previously developed homeRNA, which allows for at-home self-collection and stabilization of blood and demonstrated the feasibility of using homeRNA in high temperature climates. Here, we expand upon this work through a systematic study exploring the effects of high temperature on RNA integrity (represented as RNA Integrity Number, RIN) through in-lab and field experiments.

Neuraminidase 1 regulates neuropathogenesis by governing the cellular state of microglia via modulation of Trem2 sialylation.

Neuraminidase 1 (NEU1) cleaves terminal sialic acids from sialoglycoproteins in endolysosomes and at the plasma membrane. As such, NEU1 regulates immune cells, primarily those of the monocytic lineage. Here, we examine how Neu1 influences microglia by modulating the sialylation of full-length Trem2 (Trem2-FL), a multifunctional receptor that regulates microglial survival, phagocytosis, and cytokine production.

Ecological drivers of evolution of swine influenza in the United States: a review.

Influenza A viruses (IAVs) pose a major public health threat due to their wide host range and pandemic potential. Pigs have been proposed as "mixing vessels" for avian, swine, and human IAVs, significantly contributing to influenza ecology. In the United States, IAVs are enzootic in commercial swine farming operations, with numerous genetic and antigenic IAV variants having emerged in the past two decades.

Virus-free CRISPR knock-in of a chimeric antigen receptor into KLRC1 generates potent GD2-specific natural killer cells.

Natural killer (NK) cells are an appealing off-the-shelf, allogeneic cellular therapy due to their cytotoxic profile. However, their activity against solid tumors remains suboptimal in part due to the upregulation of NK-inhibitory ligands, such as HLA-E, within the tumor microenvironment. Here, we utilize CRISPR-Cas9 to disrupt the KLRC1 gene (encoding the HLA-E-binding NKG2A receptor) and perform non-viral insertion of a GD2-targeting chimeric antigen receptor (CAR) within NK cells isolated from human peripheral blood.

Evaluation of Cereblon-Directing Warheads for the Development of Orally Bioavailable PROTACs.

PROTACs usually occupy physicochemical space outside the one defined by classical drug-like molecules, which often presents considerable challenges in their optimization and development for oral administration. We have previously reported phenyl glutarimide (PG)-based BET PROTAC SJ995973, with improved overall degradation and antiproliferative activities compared to its direct thalidomide-based analogue dBET1, but similarly poor pharmacokinetic profile. To further demonstrate the PG utility, we describe here optimization efforts that led to the discovery of an orally bioavailable BET-PROTAC SJ44236 (), and results of a comprehensive comparative study with analogues containing alternative CRBN-directing warheads.

Nasal microbiota predictors for methicillin resistant Staphylococcus colonization in critically ill children.

Background: Surveillance cultures to identify patients colonized with methicillin-resistant Staphylococcus aureus (MRSA) is recommended at pediatric intensive care unit (PICU) admission but doesn't capture other methicillin-resistant Staphylococcus and is resource intensive. We determined the prevalence and identified nasal microbiome predictors for methicillin-resistant Staphylococcus colonization at the time of PICU admission.

Study Design: A prospective cohort study was performed in a 20-bed pediatric intensive care unit (PICU) between 2020-2021.

Challenges in determining the global burden of non-malignant central nervous system tumors: an analysis of international incidence and mortality data sources.

Background: Non-malignant tumors of the CNS contribute substantially to the morbidity and mortality from CNS tumors. It is critical to understand the epidemiology of non-malignant CNS tumors separately from CNS malignancies to inform resource allocation and policy since treatment and prognosis can differ. High quality international data on non-malignant CNS tumor burden are needed to accomplish this goal.

Transcription Factor Fingerprint Provides Clues for Brain Tumor Cell of Origin.

Mouse models that faithfully represent the biology of human brain tumors are critical tools for unraveling the underlying tumor biology and screening for potential precision therapies. This is especially true of rare tumor types, many of which have correspondingly few xenograft or cell lines available. Although our understanding of the specific biological pathways driving cancer has improved significantly, identifying the appropriate progenitor populations to drive oncogenic processes represents a significant barrier to efficient mouse model production.

Virseqimprover: an integrated pipeline for viral contig error correction, extension, and annotation.

Despite the recent surge of viral metagenomic studies, it remains a significant challenge to recover complete virus genomes from metagenomic data. The majority of viral contigs generated from de novo assembly programs are highly fragmented, presenting significant challenges to downstream analysis and inference. To address this issue, we have developed Virseqimprover, a computational pipeline that can extend assembled contigs to complete or nearly complete genomes while maintaining extension quality.

Mechanisms of chromatin remodeling by an Snf2-type ATPase.

Chromatin remodeling enzymes play a crucial role in the organization of chromatin, enabling both stability and plasticity of genome regulation. These enzymes use a Snf2-type ATPase motor to move nucleosomes, but how they translocate DNA around the histone octamer is unclear. Here we use cryo-EM to visualize the continuous motion of nucleosomal DNA induced by human chromatin remodeler SNF2H, an ISWI family member.

Non-nucleosomal (CENP-A/H4) - DNA complexes as a possible platform for centromere organization.

The centromere is a part of the chromosome that is essential for the even segregation of duplicated chromosomes during cell division. It is epigenetically defined by the presence of the histone H3 variant CENP-A. CENP-A associates specifically with a group of 16 proteins that form the centromere-associated network of proteins (CCAN).

Neuronal LAG3 facilitates pathogenic α-synuclein neuron-to-neuron propagation.

Lymphocyte activation gene 3 (LAG3) is a key receptor involved in the propagation of pathological proteins in Parkinson's disease (PD). This study investigates the role of neuronal LAG3 in mediating the binding, uptake, and propagation of α-synuclein (αSyn) preformed fibrils (PFFs). Using neuronal LAG3 conditional knockout mice and human induced pluripotent stem cells-derived dopaminergic (DA) neurons, we demonstrate that LAG3 expression is critical for pathogenic αSyn propagation.

Measuring the impact of a catchment area surveillance tool on cancer center adopters.

Background: The University of Kentucky Markey Cancer Center developed the data gathering and visualization platform Cancer InFocus (CIF) as a solution for cancer center catchment area surveillance. CIF was released in June 2022 and made available for use to other institutions through a no-cost licensing agreement. The purpose of this study was to evaluate the impact CIF has had on cancer centers since its release.

Attributable Risk and Consequences of Bone Mineral Density Deficits in Childhood Cancer Survivors.

Importance: Data characterizing the severity and changing prevalence of bone mineral density (BMD) deficits and associated nonfracture consequences among childhood cancer survivors decades after treatment are lacking.

Objective: To evaluate risk for moderate and severe BMD deficits in survivors and to identify long-term consequences of BMD deficits.

Design, Setting, And Participants: This cohort study used cross-sectional and longitudinal data from the St Jude Lifetime (SJLIFE) cohort, a retrospectively constructed cohort with prospective follow-up.

Temporal Trends of Subsequent CNS Malignancies Among Survivors of Childhood Cancer.

Purpose: It is not known whether temporal changes in childhood cancer therapy have reduced risk of subsequent malignant neoplasms (SMNs) of the central nervous system (CNS), a frequently fatal late effect of cancer therapy.

Methods: Five-year survivors of primary childhood cancers diagnosed between 1970-1999 in the Childhood Cancer Survivor Study with a subsequent CNS SMN were identified. Cumulative incidence rates and standardized incidence ratios (SIR) were compared among survivors diagnosed between 1970-1979 (N = 6223), 1980-1989 (N = 9680), and 1990-1999 (N = 8999).

Modulation of cytokeratin and cytokine/chemokine expression following influenza virus infection of differentiated human tonsillar epithelial cells.

Unlabelled: The tonsils have been identified as a site of replication for Epstein-Barr virus, adenovirus, human papillomavirus, and other respiratory viruses. Human tonsil epithelial cells (HTECs) are a heterogeneous group of actively differentiating cells. Here, we investigated the cellular features and susceptibility of differentiated HTECs to specific influenza viruses, including expression of avian-type and mammalian-type sialic acid (SA) receptors, viral replication dynamics, and the associated cytokine secretion profiles.