Analysis of time to regulatory approval in an exception from informed consent trial in trauma patients.

Background: The interactive media-based approach to community consultation and public disclosure (CC/PD), a key step when conducting exception from informed consent (EFIC) clinical trials, is intended to be completed in 4 months. This analysis characterizes the process, from initiation of CC/PD activities to institutional review board approval, to better understand the barriers and how these can be mitigated.

Methods: This is a retrospective post hoc analysis of data collected as part of the CC/PD campaigns conducted for a large trial involving up to 90 trauma centers in the United States.

Mapping the developmental trajectory of human astrocytes reveals divergence in glioblastoma.

Glioblastoma (GBM) is defined by heterogeneous and resilient cell populations that closely reflect neurodevelopmental cell types. Although it is clear that GBM echoes early and immature cell states, identifying the specific developmental programmes disrupted in these tumours has been hindered by a lack of high-resolution trajectories of glial and neuronal lineages. Here we delineate the course of human astrocyte maturation to uncover discrete developmental stages and attributes mirrored by GBM.

WebSEQ: A New Tool for Democratizing Omics Data Sharing.

The relative ease of generation and proliferation of omics datasets has moved considerably faster than the effective dissemination of these data to the scientific community. Despite advancements in making raw data publicly available, many researchers struggle with data analysis and integration. We propose sharing analyzed data through user-friendly platforms to enhance accessibility.

Implementation and validation of single-cell genomics experiments in neuroscience.

Single-cell or single-nucleus transcriptomics is a powerful tool for identifying cell types and cell states. However, hypotheses derived from these assays, including gene expression information, require validation, and their functional relevance needs to be established. The choice of validation depends on numerous factors.

Primary cilia shape postnatal astrocyte development through Sonic Hedgehog signaling.

Primary cilia function as specialized signaling centers that regulate many cellular processes including neuron and glia development. Astrocytes possess cilia, but the function of cilia in astrocyte development remains largely unexplored. Critically, dysfunction of either astrocytes or cilia contributes to molecular changes observed in neurodevelopmental disorders.

Neuron-Astrocyte Interactions: A Human Perspective.

This chapter explores the intricate interactions between neurons and astrocytes within the nervous system with a particular emphasis on studies conducted in human tissue or with human cells. We specifically explore how neuron-astrocyte interactions relate to processes of cellular development, morphology, migration, synapse formation, and metabolism. These findings enrich our understanding of basic neurobiology and how disruptions in these processes are relevant to human diseases.

Schwann cell-secreted PGE promotes sensory neuron excitability during development.

Electrical excitability-the ability to fire and propagate action potentials-is a signature feature of neurons. How neurons become excitable during development and whether excitability is an intrinsic property of neurons remain unclear. Here, we demonstrate that Schwann cells, the most abundant glia in the peripheral nervous system, promote somatosensory neuron excitability during development.

Single-cell investigation of lead toxicity from neurodevelopment to neurodegeneration: Current review and future opportunities.

Human exposure to the metal lead (Pb) is prevalent and associated with adverse neurodevelopmental and neurodegenerative outcomes. Pb disrupts normal brain function by inducing oxidative stress and neuroinflammation, altering cellular metabolism, and displacing essential metals. Prior studies on the molecular impacts of Pb have examined bulk tissues, which collapse information across all cell types, or in targeted cells, which are limited to cell autonomous effects.

Prophylactic Transfusion Strategies in Children Supported by Extracorporeal Membrane Oxygenation: The Pediatric Extracorporeal Membrane Oxygenation Anticoagulation CollaborativE Consensus Conference.

Objectives: To derive systematic-review informed, modified Delphi consensus regarding prophylactic transfusions in neonates and children supported with extracorporeal membrane oxygenation (ECMO) from the Pediatric ECMO Anticoagulation CollaborativE.

Data Sources: A structured literature search was performed using PubMed, EMBASE, and Cochrane Library (CENTRAL) databases from January 1988 to May 2020, with an update in May 2021.

Study Selection: Included studies assessed use of prophylactic blood product transfusion in pediatric ECMO.

Executive Summary: The Pediatric Extracorporeal Membrane Oxygenation Anticoagulation CollaborativE (PEACE) Consensus Conference.

Objectives: To present recommendations and consensus statements with supporting literature for the clinical management of neonates and children supported with extracorporeal membrane oxygenation (ECMO) from the Pediatric ECMO Anticoagulation CollaborativE (PEACE) consensus conference.

Data Sources: Systematic review was performed using PubMed, Embase, and Cochrane Library (CENTRAL) databases from January 1988 to May 2021, followed by serial meetings of international, interprofessional experts in the management ECMO for critically ill children.

Study Selection: The management of ECMO anticoagulation for critically ill children.

Interactive Media-Based Approach for an Exception From Informed Consent Trial Involving Patients With Trauma.

Importance: Exception From Informed Consent (EFIC) research requires community consultation (CC) and public disclosure (PD). Traditional methods of conducting CC and PD are slow, expensive, and labor intensive.

Objective: To describe the feasibility and reach of a novel interactive, media-based approach to CC and PD and to identify the similarities and differences between trial sites in website views, survey responses, online community forum attendance, and opt-out requests.

Relevance and ethical issues of diversity equity and inclusion programs, circa 2024-2025.

A recent resolution with approximately 100 signatories entitled "Sunsetting All Diversity, Equity, and Inclusion (DEI) Programs" administered by the American Academy of Dermatology (AAD) sparked controversial debate within the field. Despite the AAD voting against the proposal to eliminate DEI initiatives, many underrepresented medical groups wondered how to move forward and create safe spaces for everyone. We discuss the relevance of DEI programs in today's society and the ethical challenges that may arise.

A 3D Bioprinted Cortical Organoid Platform for Modeling Human Brain Development.

The ability to promote three-dimensional (3D) self-organization of induced pluripotent stem cells into complex tissue structures called organoids presents new opportunities for the field of developmental biology. Brain organoids have been used to investigate principles of neurodevelopment and neuropsychiatric disorders and serve as a drug screening and discovery platform. However, brain organoid cultures are currently limited by a lacking ability to precisely control their extracellular environment.

ScISOr-ATAC reveals convergent and divergent splicing and chromatin specificities between matched cell types across cortical regions, evolution, and in Alzheimer's Disease.

Multimodal measurements have become widespread in genomics, however measuring open chromatin accessibility and splicing simultaneously in frozen brain tissues remains unconquered. Hence, we devised Single-Cell-ISOform-RNA sequencing coupled with the Assay-for-Transposase-Accessible-Chromatin (ScISOr-ATAC). We utilized ScISOr-ATAC to assess whether chromatin and splicing alterations in the brain convergently affect the same cell types or divergently different ones.

Neural and metabolic dysregulation in PMM2-deficient human in vitro neural models.

Phosphomannomutase 2-congenital disorder of glycosylation (PMM2-CDG) is a rare inborn error of metabolism caused by deficiency of the PMM2 enzyme, which leads to impaired protein glycosylation. While the disorder presents with primarily neurological symptoms, there is limited knowledge about the specific brain-related changes caused by PMM2 deficiency. Here, we demonstrate aberrant neural activity in 2D neuronal networks from PMM2-CDG individuals.

Gliomas: a reflection of temporal gliogenic principles.

The hijacking of early developmental programs is a canonical feature of gliomas where neoplastic cells resemble neurodevelopmental lineages and possess mechanisms of stem cell resilience. Given these parallels, uncovering how and when in developmental time gliomagenesis intersects with normal trajectories can greatly inform our understanding of tumor biology. Here, we review how elapsing time impacts the developmental principles of astrocyte (AS) and oligodendrocyte (OL) lineages, and how these same temporal programs are replicated, distorted, or circumvented in pathological settings such as gliomas.

Histone H3 E50K mutation confers oncogenic activity and supports an EMT phenotype.

Sequencing of human patient tumors has identified recurrent missense mutations in genes encoding core histones. We report that mutations that convert histone H3 amino acid 50 from a glutamate to a lysine (H3E50K) support an oncogenic phenotype in human cells. Expression of H3E50K is sufficient to transform human cells as evidenced by a dramatic increase in cell migration and invasion, and a statistically significant increase in proliferation and clonogenicity.

Sexually Transmitted Infections and HIV in Ophthalmology.

The ocular and periocular manifestations of sexually transmitted infections (STIs) are heterogeneous in etiology, manifestations, and complications. Etiologic agents include bacteria, viruses, parasites, and protozoa, which are most frequently transmitted via direct ocular contact with an active lesion or infected bodily fluid, autoinoculation, or dissemination from a distant site. Vertical transmission most commonly occurs perinatally during vaginal delivery.