Endosomal chemokine receptor signalosomes regulate central mechanisms underlying cell migration.

Chemokine receptors are GPCRs that regulate the chemotactic migration of a wide variety of cells including immune and cancer cells. Most chemokine receptors contain features associated with the ability to stimulate G protein signaling during β-arrestin-mediated receptor internalization into endosomes. As endosomal signaling of certain non-GPCR receptors plays a major role in cell migration, we chose to investigate the potential role of endosomal chemokine receptor signaling on mechanisms governing this function.

Evaluating the radiosensitivity of the oral microbiome to predict radiation-induced mucositis in head and neck cancer patients: A prospective trial.

Background: Predicting the occurrence and/or severity of oral mucositis (OM) before commencing radiotherapy (RT) remains very difficult. The aim of this prospective trial was to investigate whether the radiation sensitivity of oral keratinocytes from head and neck (H&N) cancer patients correlates with severe OM.

Methods: Oral microbiopsies of healthy gingival mucosa were collected from 63H&N cancer patients undergoing (chemo)RT, of which 58 samples were useable.

Unfriendly neighbors: When facilitation does not contribute to restoration success in tidal marsh.

Large-scale restoration projects are an exciting and often untapped opportunity to use an experimental approach to inform ecosystem management and test ecological theory. In our $10M tidal marsh restoration project, we installed over 17,000 high marsh plants to increase cover and diversity, using these plantings in a large-scale experiment to test the benefits of clustering and soil amendments across a stress gradient. Clustered plantings have the potential to outperform widely spaced ones if plants alter conditions in ways that decrease stress for close neighbors.

Intracerebroventricular B7-H3-targeting CAR T cells for diffuse intrinsic pontine glioma: a phase 1 trial.

Diffuse intrinsic pontine glioma (DIPG) is a fatal central nervous system (CNS) tumor that confers a median survival of 11 months. As B7-H3 is expressed on pediatric CNS tumors, we conducted BrainChild-03, a single-center, dose-escalation phase 1 clinical trial of repetitive intracerebroventricular (ICV) dosing of B7-H3-targeting chimeric antigen receptor T cells (B7-H3 CAR T cells) for children with recurrent or refractory CNS tumors and DIPG. Here we report results from Arm C, restricted to patients with DIPG.

Small Molecule Modulators of β-arrestins.

Unlabelled: β-arrestins (βarrs) are key regulators of G protein-coupled receptors (GPCRs), essential for modulating signaling pathways and physiological processes. While current pharmacological strategies target GPCR orthosteric and allosteric sites, as well as G protein transducers, comparable tools for studying βarrs are lacking. Here, we present the discovery and characterization of novel small-molecule allosteric inhibitors of βarrs through comprehensive biophysical, biochemical, pharmacological, and structural analyses.

Initial treatment response can predict one-year treatment outcomes in neovascular age-related macular degeneration treated according to the observe-and-plan regimen.

Purpose: To investigate if the initial treatment response can predict the 1-year treatment outcomes in patients with neovascular age-related macular degeneration (nAMD) treated according to the observe-and-plan (O&P) regimen.

Methods: In this prospective cohort study, treatment-naïve patients with nAMD were enrolled consecutively and followed for 1 year while being treated according to the O&P regimen. The treatment response was determined initially post-loading doses and after 1 year.

Neuropilin-1 inhibition suppresses nerve growth factor signaling and nociception in pain models.

Nerve growth factor (NGF) monoclonal antibodies inhibit chronic pain, yet failed to gain approval due to worsened joint damage in osteoarthritis patients. We report that neuropilin-1 (NRP1) is a coreceptor for NGF and tropomyosin-related kinase A (TrkA) pain signaling. NRP1 was coexpressed with TrkA in human and mouse nociceptors.

Biodiversity impacts of the 2019-2020 Australian megafires.

With large wildfires becoming more frequent, we must rapidly learn how megafires impact biodiversity to prioritize mitigation and improve policy. A key challenge is to discover how interactions among fire-regime components, drought and land tenure shape wildfire impacts. The globally unprecedented 2019-2020 Australian megafires burnt more than 10 million hectares, prompting major investment in biodiversity monitoring.

Complement proteins and complement regulatory proteins are associated with age-related macular degeneration stage and treatment response.

Background: Dysregulation of the complement system is involved in development of age-related macular degeneration (AMD). The complement cascade is regulated by membrane bound complement regulatory proteins (Cregs) on mononuclear leukocytes among others. This study aims to investigate systemic complement proteins and Cregs in AMD stages and their association with treatment response in neovascular AMD (nAMD).

Validity evidence of a new virtual reality simulator for phacoemulsification training in cataract surgery.

This study aims to assess validity evidence of the new phacoemulsification module of the HelpMeSee [HMS] virtual reality simulator. Conducted at the Ophthalmology Department of Strasbourg University Hospital and Gepromed Education Department, Strasbourg, France, this cross-sectional study divided 20 surgeons into two groups based on their experience over or under 300 cataract surgeries. Surgeons filled out a background survey covering their phacoemulsification experience and prior simulator use before undergoing single-session simulations on the EyeSi [EYS] and HMS simulators.

Review of Novel Surgical, Radiation, and Systemic Therapies and Clinical Trials in Glioblastoma.

Glioblastoma (GBM) is the most common malignant primary brain tumor in adults. Despite an established standard of care including surgical resection, radiation therapy, and chemotherapy, GBM unfortunately is associated with a dismal prognosis. Therefore, researchers are extensively evaluating avenues to expand GBM therapy and improve outcomes in patients with GBM.

FATAL: A Forensic AuTopsy Annotation tooL for digital recording of autopsy findings.

The findings from forensic autopsies, where cause of death must be established and reported to legal authorities, are reported in paper-based formats. Practitioners are required to map 3D injury findings to 2D space. Here, we design and describe a digital Forensic AuTopsy Annotation tooL (FATAL), that can be used by practitioners to record systematically detailed autopsy findings onto an interactive 3D body model.

Incidentally Induced Atrial Fibrillation During Programmed Electrical Stimulation in Patients With Depressed Left Ventricular Systolic Function After an Acute Myocardial Infarction.

Background: The aim of this study was to investigate the clinical implication of incidentally induced atrial fibrillation (AF) during programmed electrical stimulation (PES) in patients with left ventricular systolic dysfunction (≤40%) after an acute myocardial infarction (MI).

Methods: In this study, we included 231 patients from the Cardiac Arrhythmias and RIsk Stratification after Myocardial InfArction (CARISMA) study with left ventricular ejection fraction ≤40% and no prior history of AF. These patients underwent PES 6 weeks post-MI as part of the study protocol.

Effects of levcromakalim in patients with migraine aura without headache: An experimental study.

Background/hypothesis: Levcromakalim has previously been shown to induce attacks of migraine with aura in certain individuals. In this study, we tested the migraine-inducing effect of levcromakalim in a cohort of participants with migraine aura without headache.

Methods: In a double-blind, randomized, placebo-controlled cross-over study, eight adult participants with migraine with aura received intravenous infusions of levcromakalim and saline.

Phacoemulsification to manual small-incision cataract surgery: transfer of skills study in a simulated environment.

Purpose: To investigate whether phacoemulsification (PE) experience impacts and transfers to the skill acquisition of novices in manual small-incision cataract surgery (MSICS) within a simulation environment.

Setting: Copenhagen Academy for Medical Education and Simulation, Copenhagen, Denmark.

Design: Prospective controlled experimental study.

Computing tools for effective field theories: SMEFT-Tools 2022 Workshop Report, 14-16th September 2022, Zürich.

In recent years, theoretical and phenomenological studies with effective field theories have become a trending and prolific line of research in the field of high-energy physics. In order to discuss present and future prospects concerning automated tools in this field, the SMEFT-Tools 2022 workshop was held at the University of Zurich from 14th-16th September 2022. The current document collects and summarizes the content of this workshop.

Role of the V2R-βarrestin-Gβγ complex in promoting G protein translocation to endosomes.

Classically, G protein-coupled receptors (GPCRs) promote signaling at the plasma membrane through activation of heterotrimeric Gαβγ proteins, followed by the recruitment of GPCR kinases and βarrestin (βarr) to initiate receptor desensitization and internalization. However, studies demonstrated that some GPCRs continue to signal from internalized compartments, with distinct cellular responses. Both βarr and Gβγ contribute to such non-canonical endosomal G protein signaling, but their specific roles and contributions remain poorly understood.

Systemic infection in aged mice causes upregulation of crystallin alpha A in the RPE/choroid.

Aging changes the responsiveness of our immune defense, and this decline in immune reactivity plays an important role in the increased susceptibility to infections that marks progressing age. Aging is also the most pronounced risk factor for development of age-related macular degeneration (AMD), a disease that is characterized by dysfunctional retinal pigment epithelial (RPE) cells and loss of central vision. We have previously shown that acute systemic viral infection has a large impact on the retina in young mice, leading to upregulation of chemokines in the RPE/choroid (RPE/c) and influx of CD8 T cells in the neuroretina.

Heterologous versus homologous COVID-19 booster vaccinations for adults: systematic review with meta-analysis and trial sequential analysis of randomised clinical trials.

Background: To combat coronavirus disease 2019 (COVID-19), booster vaccination strategies are important. However, the optimal administration of booster vaccine platforms remains unclear. Herein, we aimed to assess the benefits and harms of three or four heterologous versus homologous booster regimens.