Development of the EPO-Score - a multivariable tool to predict adverse outcome in infants with perinatal asphyxia undergoing therapeutic hypothermia - a retrospective study.

Aim: Early outcome prediction in neonates with perinatal asphyxia receiving therapeutic hypothermia (TH) remains difficult. Although several studies have explored prognostic markers and proposed scoring systems, none of these tools has been adopted for routine bedside use to date. The present retrospective study aimed to design an early prognostic outcome score (EPO-Score).

A diverse landscape of FGFR alterations and co-mutations suggests potential therapeutic strategies in pediatric low-grade gliomas.

Oncogenic alterations in fibroblast growth factor receptor (FGFR)-family proteins occur across cancers, including pediatric gliomas. Our genomic analysis of 11,635 gliomas across ages finds that 5.3% of all gliomas harbor FGFR alterations, with an incidence of almost 9% in pediatric gliomas.

Targeting the Dependence on PIK3C3-mTORC1 Signaling in Dormancy-Prone Breast Cancer Cells Blunts Metastasis Initiation.

Unlabelled: Halting breast cancer metastatic relapse following primary tumor removal remains challenging due to a lack of specific vulnerabilities to target during the clinical dormancy phase. To identify such vulnerabilities, we conducted genome-wide CRISPR screens on two breast cancer cell lines with distinct dormancy properties: 4T1 (short-term dormancy) and 4T07 (prolonged dormancy). The dormancy-prone 4T07 cells displayed a unique dependency on class III PI3K (PIK3C3).

FOXR2 Targets LHX6+/DLX+ Neural Lineages to Drive Central Nervous System Neuroblastoma.

Central nervous system neuroblastoma with forkhead box R2 (FOXR2) activation (NB-FOXR2) is a high-grade tumor of the brain hemispheres and a newly identified molecular entity. Tumors express dual neuronal and glial markers, leading to frequent misdiagnoses, and limited information exists on the role of FOXR2 in their genesis. To identify their cellular origins, we profiled the transcriptomes of NB-FOXR2 tumors at the bulk and single-cell levels and integrated these profiles with large single-cell references of the normal brain.

Immune landscape of oncohistone-mutant gliomas reveals diverse myeloid populations and tumor-promoting function.

Histone H3-mutant gliomas are deadly brain tumors characterized by a dysregulated epigenome and stalled differentiation. In contrast to the extensive datasets available on tumor cells, limited information exists on their tumor microenvironment (TME), particularly the immune infiltrate. Here, we characterize the immune TME of H3.

The Neurodevelopmental Protein POGZ Suppresses Metastasis in Triple-Negative Breast Cancer by Attenuating TGFβ Signaling.

The pogo transposable element-derived zinc finger protein, POGZ, is notably associated with neurodevelopmental disorders through its role in gene transcription. Many proteins involved in neurological development are often dysregulated in cancer, suggesting a potential role for POGZ in tumor biology. Here, we provided experimental evidence that POGZ influences the growth and metastatic spread of triple-negative breast cancers (TNBC).

SIADH as a Rare Complication of Foramen Magnum Stenosis in an Infant With Achondroplasia.

Achondroplasia is the most common skeletal dysplasia and is associated with serious complications such as foramen magnum stenosis (FMS). This case report describes an infant with achondroplasia who presented with a syndrome of inappropriate antidiuretic hormone secretion (SIADH), secondary to significant FMS and myelocompression. A 2-month-old boy with prenatally diagnosed achondroplasia was referred due to disordered breathing and altered consciousness.

Childhood cancer mutagenesis caused by transposase-derived PGBD5.

Genomic rearrangements are a hallmark of most childhood tumors, including medulloblastoma, one of the most common brain tumors in children, but their causes remain largely unknown. Here, we show that PiggyBac transposable element derived 5 (Pgbd5) promotes tumor development in multiple developmentally accurate mouse models of Sonic Hedgehog (SHH) medulloblastoma. Most Pgbd5-deficient mice do not develop tumors, while maintaining normal cerebellar development.

The Deubiquitylase Otub1 Regulates the Chemotactic Response of Splenic B Cells by Modulating the Stability of the γ-Subunit Gng2.

The ubiquitin proteasome system performs the covalent attachment of lysine 48-linked polyubiquitin chains to substrate proteins, thereby targeting them for degradation, while deubiquitylating enzymes (DUBs) reverse this process. This posttranslational modification regulates key features both of innate and adaptative immunity, including antigen presentation, protein homeostasis and signal transduction. Here we show that loss of one of the most highly expressed DUBs, Otub1, results in changes in murine splenic B cell subsets, leading to a significant increase in marginal zone and transitional B cells and a concomitant decrease in follicular B cells.

Diagnostic Utility of Interleukin-6 in Early-Onset Sepsis among Term Newborns: Impact of Maternal Risk Factors and CRP Evaluation.

(1) Background: Interleukin-6 (IL-6) levels act as an early infection marker preceding C-reactive protein (CRP) elevation. This study seeks to analyze IL-6 behavior in suspected early-onset sepsis (EOS) cases among term newborns, comparing it to that of CRP and evaluating IL-6's diagnostic utility. We also aim to assess the impact of maternal risk factors on EOS in term newborns, quantifying their influence for informed decision making.

p66ShcA promotes malignant breast cancer phenotypes by alleviating energetic and oxidative stress.

Significant efforts have focused on identifying targetable genetic drivers that support the growth of solid tumors and/or increase metastatic ability. During tumor development and progression to metastatic disease, physiological and pharmacological selective pressures influence parallel adaptive strategies within cancer cell sub-populations. Such adaptations allow cancer cells to withstand these stressful microenvironments.

"Multisystem Inflammatory Syndrome in Children"-Like Disease after COVID-19 Vaccination (MIS-V) with Potential Significance of Functional Active Autoantibodies Targeting G-Protein-Coupled Receptors (GPCR-fAAb) for Pathophysiology and Therapy.

Background: An infection with SARS-CoV-2 can trigger a systemic disorder by pathological autoimmune processes. A certain type of this dysregulation is known as Multisystemic inflammatory syndrome in children (MIS-C). However, similar symptoms may occur and have been described as Multisystemic inflammatory syndrome after SARS-CoV-2 Vaccination (MIS-V) following vaccination against SARS-CoV-2.

Migration speed of captured breast cancer subpopulations correlates with metastatic fitness.

The genetic alterations contributing to migration proficiency, a phenotypic hallmark of metastatic cells required for colonizing distant organs, remain poorly defined. Here, we used single-cell magneto-optical capture (scMOCa) to isolate fast cells from heterogeneous human breast cancer cell populations, based on their migratory ability alone. We show that captured fast cell subpopulations retain higher migration speed and focal adhesion dynamics over many generations as a result of a motility-related transcriptomic profile.

Protein arginine methyltransferase 1 regulates B cell fate after positive selection in the germinal center in mice.

Positively selected germinal center B cells (GCBC) can either resume proliferation and somatic hypermutation or differentiate. The mechanisms dictating these alternative cell fates are incompletely understood. We show that the protein arginine methyltransferase 1 (Prmt1) is upregulated in murine GCBC by Myc and mTORC-dependent signaling after positive selection.

A Compendium of Syngeneic, Transplantable Pediatric High-Grade Glioma Models Reveals Subtype-Specific Therapeutic Vulnerabilities.

Unlabelled: Pediatric high-grade gliomas (pHGG) are lethal, incurable brain tumors frequently driven by clonal mutations in histone genes. They often harbor a range of additional genetic alterations that correlate with different ages, anatomic locations, and tumor subtypes. We developed models representing 16 pHGG subtypes driven by different combinations of alterations targeted to specific brain regions.

Single substitution in H3.3G34 alters DNMT3A recruitment to cause progressive neurodegeneration.

Germline histone H3.3 amino acid substitutions, including H3.3G34R/V, cause severe neurodevelopmental syndromes.

K27M in canonical and noncanonical H3 variants occurs in distinct oligodendroglial cell lineages in brain midline gliomas.

Canonical (H3.1/H3.2) and noncanonical (H3.

Histone H3.3 K27M and K36M mutations de-repress transposable elements through perturbation of antagonistic chromatin marks.

Histone H3.3 lysine-to-methionine substitutions K27M and K36M impair the deposition of opposing chromatin marks, H3K27me3/me2 and H3K36me3/me2. We show that these mutations induce hypotrophic and disorganized eyes in Drosophila eye primordia.

Clinical Characteristics of the End-of-Life Phase in Children with Life-Limiting Diseases: Retrospective Study from a Single Center for Pediatric Palliative Care.

Background: Data on the end-of-life phase of children receiving palliative care are limited. The purpose of this study is to investigate the spectrum of symptoms of terminally ill children, adolescents, and young adults, depending on their underlying disease.

Methods: Findings are based on a 4.

STAT1 potentiates oxidative stress revealing a targetable vulnerability that increases phenformin efficacy in breast cancer.

Bioenergetic perturbations driving neoplastic growth increase the production of reactive oxygen species (ROS), requiring a compensatory increase in ROS scavengers to limit oxidative stress. Intervention strategies that simultaneously induce energetic and oxidative stress therefore have therapeutic potential. Phenformin is a mitochondrial complex I inhibitor that induces bioenergetic stress.

Dual targeting of polyamine synthesis and uptake in diffuse intrinsic pontine gliomas.

Diffuse intrinsic pontine glioma (DIPG) is an incurable malignant childhood brain tumor, with no active systemic therapies and a 5-year survival of less than 1%. Polyamines are small organic polycations that are essential for DNA replication, translation and cell proliferation. Ornithine decarboxylase 1 (ODC1), the rate-limiting enzyme in polyamine synthesis, is irreversibly inhibited by difluoromethylornithine (DFMO).