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.

The urban footprint of rural forced displacement.

The rapid growth of marginal settlements in the Global South, largely fueled by the resettlement of millions of internally displaced people (IDPs), underscores the urgent need for tailored housing solutions for these vulnerable populations. However, prevailing approaches have often relied on a one-size-fits-all model, overlooking the diverse socio-spatial realities of IDP communities. Drawing on a case study in Medellin, Colombia, where a significant portion of the population consists of forced migrants, this interdisciplinary study merges concepts from human geography and urban theory with computational methods in remote sensing and exploratory spatial data analysis.

Comparison of tissue factor-activated versus citrated native thromboelastography in dogs with suspected hemostatic abnormalities.

Viscoelastic testing methods, including thromboelastography (TEG) and rotational thromboelastometry, have an advantage over traditional tests of coagulation due to their ability to reflect in vivo hemostasis and predict need for transfusion of blood products more accurately. TEG in clinical settings is most often performed on citrated whole blood samples that are recalcified at the time of analysis, with or without the addition of an activator of coagulation. To date, superiority of the use of an activator in canine patients with abnormal hemostasis has not been demonstrated.

Impacts of women's work and childcare on child illness among Bangladeshi Shodagor communities.

For decades, women's employment has been seen as crucial for achieving greater autonomy and empowerment for women, and for promoting better health and nutrition outcomes for children, particularly in low- and middle-income countries (LMIC). However, numerous empirical studies of the relationship between women's work and child outcomes have shown mixed results. Our study tests the assumptions of a model that suggests loss of maternal care during working hours may produce negative health outcomes for children.

Pulsed-field ablation for atrial fibrillation without the use of fluoroscopy.

Introduction: Pulsed-field ablation (PFA) and fluoroless ablation (FA) are emerging techniques in contemporary in electrophysiology. With widespread use of 3D electroanatomic mapping systems and advanced intracardiac echo (ICE) imaging, fluoroless ablation has become more widely adopted. However, with the importance of tissue contact for lesion durability, initial PFA has been used with fluoroscopic guidance, but both ICE and electroanatomic mapping make fluoroless PFA feasible.

Running on Empty: Ontario Hospital Workers' Mental Health and Well-Being Deteriorating Under Austerity-Driven System.

The well-being of health care workers (HCWs) and the public in Ontario, Canada is at risk as the province's health care system is strained by neoliberal restructuring and an aging population. Deteriorating working conditions that preceded the COVID-19 pandemic further declined as the added challenges took their toll on the work force, physically and mentally. The pandemic-weary hospital staff, predominantly women, many racialized, are facing unprecedented challenges.

Carbon Recycling of High Value Bioplastics: A Route to a Zero-Waste Future.

Today, 98% of all plastics are fossil-based and non-biodegradable, and globally, only 9% are recycled. Microplastic and nanoplastic pollution is just beginning to be understood. As the global demand for sustainable alternatives to conventional plastics continues to rise, biobased and biodegradable plastics have emerged as a promising solution.

Eosinophil Depletion with Benralizumab for Eosinophilic Esophagitis.

Background: Benralizumab is an eosinophil-depleting anti-interleukin-5 receptor α monoclonal antibody. The efficacy and safety of benralizumab in patients with eosinophilic esophagitis are unclear.

Methods: In a phase 3, multicenter, double-blind, randomized, placebo-controlled trial, we assigned patients 12 to 65 years of age with symptomatic and histologically active eosinophilic esophagitis in a 1:1 ratio to receive subcutaneous benralizumab (30 mg) or placebo every 4 weeks.

Difluorinated thromboxane A reveals crosstalk between platelet activatory and inhibitory pathways by targeting both the TP and IP receptors.

Background And Purpose: Thromboxane A (TXA) is a prostanoid produced during platelet activaton, important in enhancing platelet reactivity by activation of TP receptors. However, due to the short half-life, studying TXA signalling is challenging. To enhance our understanding of TP receptor-mediated platelet biology, we therefore synthesised mono and difluorinated TXA analogues and explored their pharmacology on heterologous and endogenously expressed TP receptor function.

Individual NMDA receptor GluN2 subunit signaling domains differentially regulate the postnatal maturation of hippocampal excitatory synaptic transmission and plasticity but not dendritic morphology.

N-methyl-d-aspartate receptors (NMDARs) at hippocampal excitatory synapses undergo a late postnatal shift in subunit composition, from an initial prevalence of GluN2B subunit incorporation to a later predominance of GluN2A. This GluN2B to GluN2A shift alters NMDAR calcium conductance dynamics and intracellular molecular signaling that are individually regulated by distinct GluN2 signaling domains and temporally align with developmental alterations in dendritic and synaptic plasticity. However, the impacts of individual GluN2B to GluN2A signaling domains on neuronal development remain unknown.

Predictive phage therapy for urinary tract infections: Cocktail selection for therapy based on machine learning models.

This study supports the development of predictive bacteriophage (phage) therapy: the concept of phage cocktail selection to treat a bacterial infection based on machine learning (ML) models. For this purpose, ML models were trained on thousands of measured interactions between a panel of phage and sequenced bacterial isolates. The concept was applied to associated with urinary tract infections.

Clinical Outcomes of "Paralyzed" Nerve Transfer for Treating Spinal Cord Injury: A Proof of Concept in a Human Model.

Functional electrical stimulation (FES) is an option to restore function in individuals after high cervical spinal cord injury (SCI) who have limited available options for tendon or nerve transfer. To be considered for FES implantation, patients must possess upper motor neuron (UMN) type denervation in potential recipient muscles, which can be confirmed by response to surface electrical stimulation during clinical evaluation. Lower motor neuron (LMN) denervated muscles will not respond to electrical stimulation and, therefore, are unavailable for use in an FES system.

Using the multivariate Hawkes process to study interactions between multiple species from camera trap data.

Interspecific interactions can influence species' activity and movement patterns. In particular, species may avoid or attract each other through reactive responses in space and/or time. However, data and methods to study such reactive interactions have remained scarce and were generally limited to two interacting species.

Designing policy for Earth's urban future.

Global impacts of cities must be better conveyed to multilateral organizations.

Preoperative evaluation of nerve transfer recipients after spinal cord injury using stimulated manual muscle testing.

Nerve transfer after spinal cord injury has become increasingly popular. Accurate preoperative identification of lower motor neuron involvement in potential recipient nerves is critical. Electrodiagnostic testing has been shown to correlate with intraoperative findings; however, it is time-consuming, costly and may not be readily available.

Glioblastoma initiation, migration, and cell types are regulated by core bHLH transcription factors ASCL1 and OLIG2.

Glioblastomas (GBMs) are highly aggressive, infiltrative, and heterogeneous brain tumors driven by complex driver mutations and glioma stem cells (GSCs). The neurodevelopmental transcription factors ASCL1 and OLIG2 are co-expressed in GBMs, but their role in regulating the heterogeneity and hierarchy of GBM tumor cells is unclear. Here, we show that oncogenic driver mutations lead to dysregulation of ASCL1 and OLIG2, which function redundantly to initiate brain tumor formation in a mouse model of GBM.

How do density, employment and transit affect the prevalence of COVID-19 pandemic? A study of 3,141 counties across the United States.

Previous research has explored the effect of the built environment on the spread of the coronavirus disease (COVID-19) pandemic. This study extends the existing literature by examining the relationship between pandemic prevalence and density, employment, and transit factors at the county level. Using multilinear spatial-lag regressions and time series clustering analyses on the Smart Location Database encompassing 3141 counties in the United States, our findings reveal the following: (1) Density, employment, and transit variables yield heterogeneous effects to infection rate, death rate, and mortality rate.

Temporary Peripheral Nerve Stimulation as Treatment for Chronic Pain.

Introduction: Chronic pain is a growing problem across the world, and in the midst of an opioid epidemic, it is imperative that alternative treatment measures are identified to help alleviate the pain experienced by these patients. Chronic pain greatly affects ones quality of life and many patients do not experience adequate relief with conventional treatment measures. The purpose of this retrospective analysis is to assess the efficacy of peripheral nerve stimulation (PNS) therapy in adult patients suffering from chronic pain refractory to conventional treatment measures who underwent therapy on various anatomical locations.

Social Determinant Pathways to Hypertensive Disorders of Pregnancy Among Nulliparous U.S. Women.

Background: Hypertensive disorders of pregnancy are a leading cause of maternal morbidity and mortality in the United States and impact Black mothers at disproportionately higher rates. Hypertensive disparities among racialized groups are rooted in systemic inequalities, and we hypothesize that clinical markers of allostatic load capture embodied disparities in stressors that can link upstream social determinants of health with downstream hypertensive outcomes.

Methods: We analyzed observational cohort data from the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be (n = 6,501) and developed a structural equation model linking latent social determinants of health, longitudinal markers of allostatic load across gestation, and hypertensive pregnancy outcomes in a multigroup framework.

Temporal partitioning and the potential for avoidance behaviour within South African carnivore communities.

Carnivora occupy many ecological niches fundamental to ecosystem functioning. Within this diverse order, carnivore species compete to establish dominance, ensure survival and maintain fitness. Subordinate carnivores must, therefore, adapt their behaviour to coexist with dominant species.

Ticagrelor inverse agonist activity at the P2Y receptor is non-reversible versus its endogenous agonist adenosine 5´-diphosphate.

Background And Purpose: Ticagrelor is labelled as a reversible, direct-acting platelet P2Y receptor (P2Y R) antagonist that is indicated clinically for the prevention of thrombotic events in patients with acute coronary syndrome (ACS). As with many antiplatelet drugs, ticagrelor therapy increases bleeding risk in patients, which may require platelet transfusion in emergency situations. The aim of this study was to further examine the reversibility of ticagrelor at the P2Y R.

Radiofrequency ablation of the occipital nerves for treatment of neuralgias and headache.

Objective: The purpose of this study was to retrospectively assess the efficacy of radiofrequency ablation (RFA) therapy as a treatment for occipital neuralgias and headaches at health clinics in the United States between January 1, 2015 and June 20, 2022. We hypothesize that RFA is a minimally invasive treatment that provides significant pain relief long-term for occipital neuralgias and associated headaches.

Methods: This retrospective analysis studies data collected from 277 occipital nerve RFA patients who had adequate pre-procedure and post-procedure follow-up for data analysis.