Eye Movements and the Intraorbital Subarachnoid Space: Potential Contribution of Altered Cerebrospinal Fluid Pumping in Optic Neuropathies.

Purpose: The optic nerve (ON) is mechanically perturbed by eye movements that shift cerebrospinal fluid (CSF) within its surrounding dural sheath. This study compared changes in ON length and CSF volume within the intraorbital ON sheath caused by eye movements in healthy subjects and patients with optic neuropathies.

Methods: Twenty-one healthy controls were compared with 11 patients having primary open angle glaucoma (POAG) at normal intraocular pressure (IOP), and 11 with chronic non-arteritic anterior ischemic optic neuropathy (NA-AION).

Erwinia phage Asesino is a nucleus-forming phage that lacks PhuZ.

As nucleus-forming phages become better characterized, understanding their unifying similarities and unique differences will help us understand how they occupy varied niches and infect diverse hosts. All identified nucleus-forming phages fall within the Chimalliviridae family and share a core genome of 68 unique genes including chimallin, the major nuclear shell protein. A well-studied but non-essential protein encoded by many nucleus-forming phages is PhuZ, a tubulin homolog which aids in capsid migration, nucleus rotation, and nucleus positioning.

Assessing the scalability of health system interventions in Africa: protocol for a Delphi study.

Background: There is widespread enthusiasm for scaling interventions to strengthen health systems. However, little is known about the scalability of such interventions in Africa. In this study, we seek to assess the scalability of interventions for improving the functionality of health systems in Africa, as a key to large-scale implementation strategy of interventions with potential for impact.

Human AI collaboration for unsupervised categorization of live surgical feedback.

Formative verbal feedback during live surgery is essential for adjusting trainee behavior and accelerating skill acquisition. Despite its importance, understanding optimal feedback is challenging due to the difficulty of capturing and categorizing feedback at scale. We propose a Human-AI Collaborative Refinement Process that uses unsupervised machine learning (Topic Modeling) with human refinement to discover feedback categories from surgical transcripts.

Artificial intelligence applications in ophthalmic optical coherence tomography: a 12-year bibliometric analysis.

Aim: To explore the current application and research frontiers of global ophthalmic optical coherence tomography (OCT) imaging artificial intelligence (AI) research.

Methods: The citation data were downloaded from the Web of Science Core Collection database (WoSCC) to evaluate the articles in application of AI in ophthalmic OCT published from January 1, 2012 to December 31, 2023. This information was analyzed using CiteSpace 6.

Comparative Effectiveness of Cell-Based Versus Egg-Based Influenza Vaccines in Prevention of Influenza Hospitalization During the 2022-2023 Season Among Adults 18-64 Years.

This retrospective cohort study evaluated the comparative vaccine effectiveness (cVE) of licensed standard-dose cell-based versus egg-based influenza vaccines in preventing influenza hospitalization among adults 18-64 years during the 2022-2023 season. The cohort included eligible Kaiser Permanente Southern California members who received ≥ 1 dose of influenza vaccine (n = 848,334). The adjusted cVE against influenza hospitalization was -10.

Heteroaryl Glutarimides and Dihydrouracils as Cereblon Ligand Scaffolds for Molecular Glue Degrader Discovery.

Stabilization of cereblon (CRBN)/neosubstrate complexes with molecular glues followed by degradation of those neosubstrates is an emerging strategy in drug discovery with compelling potential to target certain proteins that were previously considered to be undruggable. In this context, the discovery of novel CRBN ligands is an important area of ongoing research that holds promise to expand the scope of proteins that can be targeted through this mode of action. Herein, we describe the synthesis and evaluation of CRBN ligands featuring heteroaryl glutarimide and dihydrouracil scaffolds.

A quantitative multi-parameter mapping protocol standardized for clinical research in multiple sclerosis.

Quantitative magnetic resonance imaging (qMRI) involves mapping microstructure in standardized units sensitive to histological properties and supplements conventional MRI, which relies on contrast weighted images where intensities have no biophysical meaning. While measuring tissue properties such as myelin, iron or water content is desired in a disease context, qMRI changes may typically reflect mixed influences from aging or pre-clinical degeneration. We used a fast multi-parameter mapping (MPM) protocol for clinical routine at 3T to reconstruct whole-brain quantitative maps of magnetization transfer saturation (MT), proton density (PD), longitudinal (R1), and transverse relaxation rate (R2*) with 1.

Influenza vaccine effectiveness against hospitalizations and emergency department or urgent care encounters for children, adolescents, and adults during the 2023-2024 season, United States.

Background: The 2023-2024 influenza season had predominant influenza A(H1N1)pdm09 virus activity, but A(H3N2) and B viruses co-circulated. Seasonal influenza vaccine strains were well-matched to these viruses.

Methods: Using health care encounters data from health systems in 8 states, we evaluated influenza vaccine effectiveness (VE) against influenza-associated medical encounters from October 2023-April 2024.

Territorial and Non-Territorial Subpopulations of Wilson's Warblers Return to Central California Breeding Grounds in Two Migratory Waves.

Early migratory return for territorial passerines is important, since earlier return results in better territories, and greater reproductive success. Many passerine studies have found that migratory return dates for first-breeding-season (SY) individuals was a week or less later than for older (ASY) birds. Many of both ASY and SY birds in these studies became territorial, although more SY than ASY birds became non-territorial floaters.

Multicenter Clinical Performance Evaluation of the NeuMoDx™ CT/NG Assay 2.0.

Background: Given the continued increases in rates of both Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infection, additional diagnostic assays may be useful in increasing access to testing for these sexually transmitted infections. We evaluated the performance of the NeuMoDx™ CT/NG Assay 2.0 on the NeuMoDx-96 and NeuMoDx-288 Molecular Systems.

Prolonged Venous Transit on Perfusion Imaging is Associated with Longer Lengths of Stay in Acute Large Vessel Occlusions.

Background And Purpose: Prolonged venous transit (PVT+) is a marker of venous outflow; it is defined as the presence or absence of time-to-maximum ≥10 seconds timing in either the superior sagittal sinus or torcula. This novel perfusion imaging-based metric has been associated with higher odds of mortality and lower odds of functional recovery. This study aims to assess the relationship between PVT on admission perfusion imaging and length of hospital stay in large vessel occlusion strokes successfully reperfused with mechanical thrombectomy.

Genome Sequence of Phage .

Phage JanetJ was isolated on and has siphovirus morphology. JanetJ's genome consists of 36,986 base pairs, encoding 52 putative protein-coding genes. JanetJ adds to the small number of previously isolated cluster FO phages, none of which encode identifiable immunity repressor or integrase functions, with the exception of phage Maja.

Single cell and TCR analysis of immune cells from AAV gene therapy-dosed Duchenne muscular dystrophy patients.

Clinical trials for Duchenne muscular dystrophy (DMD) are assessing the therapeutic efficacy of systemically delivered adeno-associated virus (AAV) carrying a modified transgene. High vector doses (>1E14 vg/kg) are needed to globally transduce skeletal muscles; however, such doses trigger immune-related adverse events. Mitigating these immune responses is crucial for widespread application of AAV-based therapies.

Gaps in biomedical research in frontotemporal dementia: A call for diversity and disparities focused research.

Frontotemporal dementia (FTD) is one of the leading causes of young-onset dementia before age 65, typically manifesting as abnormal behavior (in behavioral variant FTD) or language impairment (in primary progressive aphasia). Although FTD affects all populations across the globe, knowledge regarding the pathophysiology and genetics derives primarily from studies conducted in North America and Western Europe. Globally, biomedical research for FTD is hindered by variable access to diagnosis, discussed in this group's earlier article, and by reduced access to expertise, funding, and infrastructure.

Effects of Extracted Pulse Proteins on Lipid Targets for Cardiovascular Risk Reduction: Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: Many clinical practice guidelines recommend dietary pulses for the prevention and management of cardiovascular disease and diabetes. The impact of extracted pulse proteins remains unclear. We therefore conducted a systematic review and meta-analysis of randomized controlled trials of the effect of extracted pulse proteins on therapeutic lipid targets.

Mutant-selective AKT inhibition through lysine targeting and neo-zinc chelation.

Somatic alterations in the oncogenic kinase AKT1 have been identified in a broad spectrum of solid tumours. The most common AKT1 alteration replaces Glu17 with Lys (E17K) in the regulatory pleckstrin homology domain, resulting in constitutive membrane localization and activation of oncogenic signalling. In clinical studies, pan-AKT inhibitors have been found to cause dose-limiting hyperglycaemia, which has motivated the search for mutant-selective inhibitors.

VEGF inhibition increases expression of HIF-regulated angiogenic genes by the RPE limiting the response of wet AMD eyes to aflibercept.

Neovascular age-related macular degeneration (nvAMD) is the leading cause of severe vision loss in the elderly in the developed world. While the introduction of therapies targeting vascular endothelial growth factor (VEGF) has provided the first opportunity to significantly improve vision in patients with nvAMD, many patients respond inadequately to current anti-VEGF therapies. It was recently demonstrated that expression of a second angiogenic mediator, angiopoietin-like 4 (ANGPTL4), synergizes with VEGF to promote choroidal neovascularization (CNV) in mice and correlates with reduced response to anti-VEGF therapy in patients with nvAMD.

The potential of muscarinic M and M receptor activators for the treatment of cognitive impairment associated with schizophrenia.

Cognitive impairment is a core symptom of schizophrenia and a major determinant of poor long-term functional outcomes. Despite considerable efforts, we do not yet have any approved pharmacological treatments for cognitive impairment associated with schizophrenia (CIAS). A combination of advances in pre-clinical research and recent clinical trial findings have led to a resurgence of interest in the cognition-enhancing potential of novel muscarinic acetylcholine receptor (mAChR) agonists in schizophrenia.

Role of Hypoperfusion Intensity Ratio in Vessel Occlusions: A Review on Safety and Clinical Outcomes.

The hypoperfusion intensity ratio (HIR) is a quantitative metric used in vascular occlusion imaging to evaluate the extent of brain tissue at risk due to hypoperfusion. Defined as the ratio of tissue volume with a time-to-maximum (Tmax) of >10 seconds to that of >6 seconds, HIR assists in differentiating between the salvageable penumbra and the irreversibly injured core infarct. This review explores the role of HIR in assessing clinical outcomes and guiding treatment strategies, including mechanical thrombectomy and thrombolytic therapy, for patients with large vessel occlusions (LVOs).

SLC16A8 is a causal contributor to age-related macular degeneration risk.

Age-related macular degeneration (AMD), a complex neurodegenerative disease, is a leading cause of visual impairment worldwide with a strong genetic component. Genetic studies have identified several loci, but few causal genes with functional characterization. Here we highlight multiple lines of evidence which show a causal role in AMD for SLC16A8, which encodes MCT3, a retinal pigment epithelium (RPE) specific lactate transporter.