Transcription factors ASCL1 and OLIG2 drive glioblastoma initiation and co-regulate tumor cell types and migration.

Glioblastomas (GBMs) are highly aggressive, infiltrative, and heterogeneous brain tumors driven by complex genetic alterations. The basic-helix-loop-helix (bHLH) transcription factors ASCL1 and OLIG2 are dynamically co-expressed in GBMs; however, their combinatorial roles in regulating the plasticity and heterogeneity of GBM cells are unclear. Here, we show that induction of somatic mutations in subventricular zone (SVZ) progenitor cells leads to the dysregulation of ASCL1 and OLIG2, which then function redundantly and are required for brain tumor formation in a mouse model of GBM.

Antibody-Fab and -Fc features promote restriction.

the causative agent of tuberculosis (TB), is a leading cause of death by an infectious disease globally, with no efficacious vaccine. Antibodies are implicated in control, but the mechanisms of antibody action remain poorly understood. We assembled a library of TB monoclonal antibodies (mAb) and screened for the ability to restrict in mice, identifying protective antibodies targeting known and novel antigens.

DOR activation in mature oligodendrocytes regulates α-ketoglutarate metabolism leading to enhanced remyelination in aged mice.

The decreased ability of mature oligodendrocytes to produce myelin negatively affects remyelination in demyelinating diseases and aging, but the underlying mechanisms are incompletely understood. In the present study, we identify a mature oligodendrocyte-enriched transcriptional coregulator diabetes- and obesity-related gene (DOR)/tumor protein p53-inducible nuclear protein 2 (TP53INP2), downregulated in demyelinated lesions of donors with multiple sclerosis and in aged oligodendrocyte-lineage cells. Dor ablation in mice of both sexes results in defective myelinogenesis and remyelination.

Toxicity and decomposition activity inhibition of VO micro/nanoparticles to white rot fungus Phanerochaete chrysosporium.

Vanadium dioxide (VO) is an excellent phase transition material widely used in various applications, and thus inevitably enters the environment via different routes and encounters various organisms. Nonetheless, limited information is available on the environmental hazards of VO. In this study, we investigated the impact of two commercial VO particles, nanosized S-VO and micro-sized M-VO on the white rot fungus Phanerochaete chrysosporium.

Shared patterns of glial transcriptional dysregulation link Huntington's disease and schizophrenia.

Huntington's disease and juvenile-onset schizophrenia have long been regarded as distinct disorders. However, both manifest cell-intrinsic abnormalities in glial differentiation, with resultant astrocytic dysfunction and hypomyelination. To assess whether a common mechanism might underlie the similar glial pathology of these otherwise disparate conditions, we used comparative correlation network approaches to analyse RNA-sequencing data from human glial progenitor cells (hGPCs) produced from disease-derived pluripotent stem cells.

Small-molecule-induced epigenetic rejuvenation promotes SREBP condensation and overcomes barriers to CNS myelin regeneration.

Remyelination failure in diseases like multiple sclerosis (MS) was thought to involve suppressed maturation of oligodendrocyte precursors; however, oligodendrocytes are present in MS lesions yet lack myelin production. We found that oligodendrocytes in the lesions are epigenetically silenced. Developing a transgenic reporter labeling differentiated oligodendrocytes for phenotypic screening, we identified a small-molecule epigenetic-silencing-inhibitor (ESI1) that enhances myelin production and ensheathment.

The myelination-associated G protein-coupled receptor 37 is regulated by Zfp488, Nkx2.2, and Sox10 during oligodendrocyte differentiation.

Oligodendrocyte differentiation and myelination in the central nervous system are controlled and coordinated by a complex gene regulatory network that contains several transcription factors, including Zfp488 and Nkx2.2. Despite the proven role in oligodendrocyte differentiation little is known about the exact mode of Zfp488 and Nkx2.

Small bites versus large bites during fascial closure of midline laparotomies: a systematic review and meta-analysis.

Purpose: Incisional ventral hernias (IVH) are common after laparotomies, with up to 20% incidence in 12 months, increasing up to 60% at 3-5 years. Although Small Bites (SB) is the standard technique for fascial closure in laparotomies, its adoption in the United States is limited, and Large Bites (LB) is still commonly performed. We aim to assess the effectiveness of SB regarding IVH.

Facial Nerve Considerations for the Deep Plane Facelift and Neck Lift.

The surgical approach to facial rejuvenation has evolved significantly over the last century. As surgeons have deepened their understanding of facial anatomy over the last half century, so have their surgical approaches to the rhytidectomy, with increasingly extensive manipulation of the underlying soft tissue in the face. While these procedures have become more comprehensive and natural in their approach, the risk of temporary facial palsy also appears to be on the rise.

Chaetocin-mediated SUV39H1 inhibition targets stemness and oncogenic networks of diffuse midline gliomas and synergizes with ONC201.

Background: Diffuse intrinsic pontine gliomas (DIPG/DMG) are devastating pediatric brain tumors with extraordinarily limited treatment options and uniformly fatal prognosis. Histone H3K27M mutation is a common recurrent alteration in DIPG and disrupts epigenetic regulation. We hypothesize that genome-wide H3K27M-induced epigenetic dysregulation makes tumors vulnerable to epigenetic targeting.

PathDIP 5: improving coverage and making enrichment analysis more biologically meaningful.

Pathway Data Integration Portal (PathDIP) is an integrated pathway database that was developed to increase functional gene annotation coverage and reduce bias in pathway enrichment analysis. PathDIP 5 provides multiple improvements to enable more interpretable analysis: users can perform enrichment analysis using all sources, separate sources or by combining specific pathway subsets; they can select the types of sources to use or the types of pathways for the analysis, reducing the number of resulting generic pathways or pathways not related to users' research question; users can use API. All pathways have been mapped to seven representative types.

Beyond-66: A pilot evaluation of a novel, peer-led harm reduction intervention for chemsex dependant men who have sex with men in Kuala Lumpur, Malaysia.

Background: There is little research exploring harm reduction interventions for men who have sex with men (MSM) who engage in chemsex. Beyond-66 is a novel, 132-day, peer-led intervention programme for MSM who are chemsex dependent in Kuala Lumpur, Malaysia. We aimed to evaluate the feasibility, retention and effect of Beyond-66 on: abstinence from chemsex, motivation for abstinence, and mental wellbeing.

Body Mass Index Effect on Minimally Invasive Ventral Hernia Repair: A Systematic Review and Meta-analysis.

Purpose: Obesity is one of the most important risk factors for complications after ventral hernia repair (VHR), and minimally invasive (MIS) techniques are preferred in obese patients as they minimize wound complications. It is common practice to attempt weight loss to achieve a specific body mass index (BMI) goal; however, patients are often unable to reach it and fail to become surgical candidates. Therefore, we aim to perform a meta-analysis of studies comparing outcomes of obese and nonobese patients undergoing laparoscopic or robotic VHR.

Distinct requirements for Tcf3 and Tcf12 during oligodendrocyte development in the mouse telencephalon.

Background: E-proteins encoded by Tcf3, Tcf4, and Tcf12 are class I basic helix-loop-helix (bHLH) transcription factors (TFs) that are thought to be widely expressed during development. However, their function in the developing brain, specifically in the telencephalon remains an active area of research. Our study examines for the first time if combined loss of two E-proteins (Tcf3 and Tcf12) influence distinct cell fates and oligodendrocyte development in the mouse telencephalon.

Heavyweight versus non-heavyweight mesh in ventral hernia repair: a systematic review and meta-analysis.

Purpose: There is considerable variability among surgeons regarding the type of mesh used in ventral hernia repair. There has been an increasing incidence of mesh fractures with lightweight (LW) and mediumweight (MW) meshes. However, HW mesh has been associated with a greater foreign body sensation and chronic pain.

Risk of inpatient epistaxis admission related to oral anticoagulation medication use.

We utilized a case control study to determine if novel oral anticoagulants were associated with a higher risk of inpatient epistaxis admission. Adult patients admitted with a principal diagnosis of epistaxis in 2019-2021 were identified as well as a control group of patients matched 1:1 for age, sex, race, and medical comorbidities. For both cohorts, the presence or absence of an oral anticoagulant, classified as vitamin K inhibitors, direct oral anticoagulants (DOAC) or platelet inhibitors, was identified.

Physiological and evolutionary contexts of a new symbiotic species from the nitrogen-recycling gut community of turtle ants.

While genome sequencing has expanded our knowledge of symbiosis, role assignment within multi-species microbiomes remains challenging due to genomic redundancy and the uncertainties of in vivo impacts. We address such questions, here, for a specialized nitrogen (N) recycling microbiome of turtle ants, describing a new genus and species of gut symbiont-Ischyrobacter davidsoniae (Betaproteobacteria: Burkholderiales: Alcaligenaceae)-and its in vivo physiological context. A re-analysis of amplicon sequencing data, with precisely assigned Ischyrobacter reads, revealed a seemingly ubiquitous distribution across the turtle ant genus Cephalotes, suggesting ≥50 million years since domestication.

The Subglottic Stenosis 6 Questionnaire: A Novel Quality-of-Life Survey Validated to Predict Need for Intervention in Patients With Idiopathic Subglottic Stenosis.

Background: Idiopathic subglottic stenosis (iSGS) is a recurrent, chronic disease defined by fibroinflammatory narrowing of the subglottic airway. A key challenge in treatment is monitoring disease progression, which may be debilitating and unpredictable in its timing.

Research Question: Can the Subglottic Stenosis 6 (SGS-6) questionnaire be validated as a novel quality-of-life (QOL) instrument to monitor breathing, disease progression, and disease severity proactively in patients with iSGS?

Study Design And Methods: Panel data from 51 patients with iSGS were collected from January 2012 through June 2022, representing 1,684 patient encounters including routine office visits and treatment encounters.