Hyperactive neuronal networks facilitate tau spread in an Alzheimer's disease mouse model.

Pathological tau spreads throughout the brain along neuronal connections in Alzheimer's disease (AD), but the mechanisms that underlie this process are poorly understood. Given the high incidence and deleterious consequences of epileptiform activity in AD, we hypothesized neuronal hyperactivity and seizures are key factors in tau spread. To examine these interactions, we created a novel mouse model involving the cross of targeted recombination in active populations (TRAP) mice and the 5 times familial AD (5XFAD; 5X-TRAP) model allowing for the permanent fluorescent labelling of neuronal activity.

Capping Effects on Spin and Charge Excitations in Parent and Superconducting Nd_{1-x}Sr_{x}NiO_{2}.

Superconductivity in infinite layer nickelates Nd_{1-x}Sr_{x}NiO_{2} has so far been achieved only in thin films, raising questions on the role of substrates and interfaces. Given the challenges associated with their synthesis it is imperative to identify their intrinsic properties. We use resonant inelastic x-ray scattering to investigate the influence of the SrTiO_{3} capping layer on the excitations of Nd_{1-x}Sr_{x}NiO_{2} (x=0 and 0.

Impact of Myc-Altered Pathology on Radiation Therapy Efficacy Among Patients With Relapsed/Refractory Large-B Cell Lymphoma: A Collaborative Study by ILROG.

Purpose: The presence of MYC and BCL2 translocations (ie, double-hit lymphoma, DHL) in large B-cell lymphoma (LBCL) is associated with reduced chemosensitivity, but less is known on its impact on radiotherapy (RT) efficacy.

Methods And Materials: Patients with LBCL who received their first course of RT for relapsed/refractory disease between 2008 and 2020 were eligible if there was adequate pathologic evaluation to be categorized as DHL versus non-DHL as per the World Health Organization (fifth edition). Separate analyses were conducted by treatment intent.

Spatial intra-tumour heterogeneity and treatment-induced genomic evolution in oesophageal adenocarcinoma: implications for prognosis and therapy.

Background: Oesophageal adenocarcinoma (OAC) is a highly heterogeneous cancer with poor survival. Standard curative treatment is chemotherapy with or without radiotherapy followed by oesophagectomy. Genomic heterogeneity is a feature of OAC and has been linked to treatment resistance.

Mechanistic investigations of the Fe(ii) mediated synthesis of squaraines.

The scission and homologation of CO is a fundamental process in the Fischer-Tropsch reaction. However, given the heterogeneous nature of the catalyst and forcing reaction conditions, it is difficult to determine the intermediates of this reaction. Here we report detailed mechanistic insight into the scission/homologation of CO by two-coordinate iron terphenyl complexes.

Relatively stable pressure effects and time-increasing thermal contraction control Heber geothermal field deformation.

Due to geological complexities and observational gaps, it is challenging to identify the governing physical processes of geothermal field deformation including ground subsidence and earthquakes. In the west and east regions of the Heber Geothermal Field (HGF), decade-long subsidence was occurring despite injection of heat-depleted brines, along with transient reversals between uplift and subsidence. These observed phenomena contradict current knowledge that injection leads to surface uplift.

Achieving a textbook outcome in patients undergoing gastric resections in a low incidence, high-volume Australian Upper GI unit.

Background: Textbook outcome (TBO) has been proposed as a composite measure of quality in esophagogastric surgery, and achieving a TBO has been associated with improved overall survival (OS). The Dutch Upper Gastrointestinal Cancer Audit group determined their TBO rate for gastrectomy to be 32.1%, using 10 parameters.

Seizures exacerbate excitatory: inhibitory imbalance in Alzheimer's disease and 5XFAD mice.

Approximately 22% of Alzheimer's disease (AD) patients suffer from seizures, and the co-occurrence of seizures and epileptiform activity exacerbates AD pathology and related cognitive deficits, suggesting that seizures may be a targetable component of AD progression. Given that alterations in neuronal excitatory:inhibitory (E:I) balance occur in epilepsy, we hypothesized that decreased markers of inhibition relative to those of excitation would be present in AD patients. We similarly hypothesized that in 5XFAD mice, the E:I imbalance would progress from an early stage (prodromal) to later symptomatic stages and be further exacerbated by pentylenetetrazol (PTZ) kindling.

Pediatric Anesthesia Exposure: Decoding Its Neurodevelopmental Implications and Navigating the Nuances.

General anesthesia is fundamental in pediatric medical interventions, but its potential neurodevelopmental impact on children has raised concerns, necessitating a thorough investigation. This systematic review aimed to assess the association between pediatric anesthesia exposure and neurodevelopmental outcomes, focusing on dosage effects and identifying high-risk groups. The study involved an extensive literature search across PubMed, Medline, and Google Scholar, selecting 40 relevant studies from an initial pool of 2,000, based on inclusion criteria that focused on children under 18 years exposed to anesthesia, excluding those with major comorbidities or perioperative physiological insults.

Practical 10-Color T-Cell Panel for Phenotyping Diverse Populations Using Spectral Flow Cytometry: A Beginner's Guide.

Flow cytometry stands as the most employed high-throughput single-cell analysis technique, facilitating the profiling of remarkably diverse samples, such as blood, bone marrow and body fluids. In addition, it allows for the discrimination of diverse immune cell subsets, including infrequently encountered types like T regulatory cells and exhausted CD28 T cells. However, analyzing rare immune cell subsets with conventional flow cytometry poses challenges stemming from factors like fluorophore overlap, compensation issues, and limited flexibility in fluorophore selection.

Prognostic value of cerebrospinal fluid tumor cell count in leptomeningeal disease from solid tumors.

Purpose: Treatment decisions for leptomeningeal disease (LMD) rely on patient risk stratification, since clinicians lack objective prognostic tools. The introduction of rare cell capture technology for identification of cerebrospinal fluid tumor cells (CSF-TCs), such as CNSide assay, improved the sensitivity of LMD diagnosis, but prognostic value is unknown. This study assesses the prognostic value of CSF-TC density in patients with LMD from solid tumors.

Radiation Therapy in the Management of Leptomeningeal Disease From Solid Tumors.

Purpose: Leptomeningeal disease (LMD) is clinically detected in 5% to 10% of patients with solid tumors and is a source of substantial morbidity and mortality. Prognosis for this entity remains poor and treatments are palliative. Radiation therapy (RT) is an essential tool in the management of LMD, and a recent randomized trial demonstrated a survival benefit for proton craniospinal irradiation (CSI) in select patients.

iCare - a self-directed, interactive online program to improve health and wellbeing for people living with upper gastrointestinal or hepato-pancreato-biliary cancers, and their informal carers: the study protocol for a Phase II randomised controlled trial.

Background: Up to 70% of people diagnosed with upper gastrointestinal (GI) tract or hepato-pancreato-biliary (HPB) cancers experience substantial reductions in quality of life (QoL), including high distress levels, pain, fatigue, sleep disturbances, weight loss and difficulty swallowing. With few advocacy groups and support systems for adults with upper GI or HPB cancers (i.e.

Reversible synaptic adaptations in a subpopulation of murine hippocampal neurons following early-life seizures.

Early-life seizures (ELSs) can cause permanent cognitive deficits and network hyperexcitability, but it is unclear whether ELSs induce persistent changes in specific neuronal populations and whether these changes can be targeted to mitigate network dysfunction. We used the targeted recombination of activated populations (TRAP) approach to genetically label neurons activated by kainate-induced ELSs in immature mice. The ELS-TRAPed neurons were mainly found in hippocampal CA1, remained uniquely susceptible to reactivation by later-life seizures, and displayed sustained enhancement in α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor-mediated (AMPAR-mediated) excitatory synaptic transmission and inward rectification.

Leveraging spatial omics for the development of precision sarcoma treatments.

Sarcomas are rare and heterogeneous cancers that arise from bone or soft tissue, and are the second most prevalent solid cancer in children and adolescents. Owing to the complex nature of pediatric sarcomas, the development of therapeutics for pediatric sarcoma has seen little progress in the past decades. Existing treatments are largely limited to chemotherapy, radiation, and surgery.

The infection-tolerant white-footed deermouse tempers interferon responses to endotoxin in comparison to the mouse and rat.

The white-footed deermouse , a long-lived rodent, is a key reservoir in North America for agents of several zoonoses, including Lyme disease, babesiosis, anaplasmosis, and a viral encephalitis. While persistently infected, this deermouse is without apparent disability or diminished fitness. For a model for inflammation elicited by various pathogens, the endotoxin lipopolysaccharide (LPS) was used to compare genome-wide transcription in blood by , and and adjusted for white cell concentrations.

What is the annual risk of infection in congenital midline neck cysts in children? Thyroglossal duct cysts versus dermoid cysts.

Introduction: Midline neck lumps in children are mostly found to be thyroglossal duct cysts or dermoid cysts. Thyroglossal duct cysts often have an associated sinus tract which may connect all the way to the foramen caecum on the tongue, while dermoids have no such connection. This study aims to estimate the annual infection risk for midline neck cysts based on our patient series, and to see if this differs between thyroglossal duct cysts and dermoid cysts.

Tumour microenvironment influences response to treatment in oesophageal adenocarcinoma.

The poor treatment response of oesophageal adenocarcinoma (OAC) leads to low survival rates. Its increasing incidence makes finding more effective treatment a priority. Recent treatment improvements can be attributed to the inclusion of the tumour microenvironment (TME) and immune infiltrates in treatment decisions.

The oesophageal adenocarcinoma tumour immune microenvironment dictates outcomes with different modalities of neoadjuvant therapy - results from the AGITG DOCTOR trial and the cancer evolution biobank.

A plateau in treatment effect can be seen for the current 'one-size-fits-all' approach to oesophageal adenocarcinoma (OAC) management using neoadjuvant chemoradiotherapy (nCRT) or chemotherapy (nCT). In OAC, the tumour microenvironment (TME) is largely immunosuppressed, however a subgroup of patients with an immune-inflamed TME exist and show improved outcomes. We aimed to understand the overall immune-based mechanisms underlying treatment responses and patient outcomes in OAC, and in relation to neoadjuvant therapy modality.

Emergent radiotherapy for spinal cord compression/impingement-a narrative review.

Background And Objective: Malignant epidural spinal cord compression (MESCC), often presenting with back pain and motor/sensory deficits, is associated with poor survival, particularly when there is loss of ambulation. The purpose of this review is to evaluate the literature and discuss appropriate workup and management of MESCC, specifically in the emergent setting.

Methods: A PubMed search was conducted on "spinal cord compression" and "radiation therapy.