Evaluating the reliability of a microperimetry-based method for assessing visual function in the junctional zone of geographic atrophy lesions.

Purpose: To assess the repeatability of a microperimetry methodology for quantifying visual function changes in the junctional zone of eyes with geographic atrophy (GA) in the clinical trial context.

Methods: A post hoc analysis of the OAKS phase III trial was conducted, which enrolled patients with GA secondary to age-related macular degeneration. Microperimetry using a standard 10 - 2 fovea centered grid was performed at baseline and follow-up visits.

Evaluating the Reliability of a Microperimetry-Based Method for Assessing Visual Function in the Junctional Zone of Geographic Atrophy Lesions.

Purpose: To assess the repeatability of a microperimetry methodology for quantifying visual function changes in the junctional zone of eyes with geographic atrophy (GA) in the clinical trial context.

Methods: A post hoc analysis of the OAKS phase III trial was conducted, which enrolled patients with GA secondary to age-related macular degeneration. Microperimetry using a standard 10-2 fovea centered grid was performed at baseline and follow-up visits.

Impact of Ultrasound- and Microwave-Assisted Extraction on Bioactive Compounds and Biological Activities of and .

This study represents the first investigation into the ultrasonic and microwave extraction of bioactive metabolites from (red seaweed) and () (brown seaweed), with a focus on their biological activities. The research compares ultrasound-assisted extraction (UAE) with microwave-assisted extraction (MAE) utilizing a hydromethanolic solvent to evaluate their effects on these seaweeds' bioactive compounds and biological activities. The assessment included a series of antioxidant essays: DPPH, ABTS, phenanthroline, and total antioxidant capacity, followed by enzyme inhibition activities: alpha-amylase and urease.

Fifteen-Year Radiographic Follow-up Comparison of Early Versus Delayed ACL Reconstruction: A Retrospective Review of a Previous Prospective Randomized Clinical Trial.

Background: Posttraumatic osteoarthritis (PTOA) after anterior cruciate ligament injury and reconstruction (ACLR) is a prevalent cause of long-term disability. Few studies have compared the effect of ACLR timing on the development of PTOA.

Purpose/hypothesis: The purpose of this study was to compare the rate of PTOA at a long-term follow-up between patients who underwent early ACLR (<21 days after injury) versus delayed ACLR (>6 weeks after injury).

Diagnosis, treatment, and follow-up of patients with hypophosphatasia.

Introduction: Hypophosphatasia is a rare inherited systemic metabolic disorder, with an estimated prevalence in the severe forms of the disease of 1/100.000-1/300.000, that affects the typical architecture of bone, leading to defective mineralization during growth and remodeling.

Definitive Evidence for the Identification and Function of Renin-Expressing Cholinergic Neurons in the Nucleus Ambiguus.

Background: The importance of the brain renin-angiotensin system in cardiovascular function is well accepted. However, not knowing the precise source of renin in the brain has been a limitation toward a complete understanding of how the brain renin-angiotensin system operates.

Methods: Highly sensitive in situ hybridization techniques and conditional knockout mice were used to address the location and function of renin in the brainstem.

Longitudinal Assessment of Retinopathy of Prematurity (LONGROP) Study: Impacts of Viewing Time and Ability to Compare on Detection of Change.

Purpose: This study compared two imaging grading techniques to assess the utility of longitudinal image-based analysis in retinopathy of prematurity (ROP) screening: (1) time-limited without image comparison (a proxy for bedside indirect ophthalmoscopy, termed sBIO) and time-unlimited with image comparison (for telemedicine grading, termed TELE) screening. We tested two hypotheses: (1) H1: TELE was superior to sBIO for the detection of change (Tempo)-same, better, or worse and (2) H2: granular data of change (e.g.

Let's get functional: Drug sensitivity profiling to enable precision sarcoma medicine.

Drug sensitivity profiling in patient-derived tumor models offers new hope for improving outcomes in cancers lacking effective therapies. Al Shihabi et al. demonstrate that short-term cultures from bone and soft tissue sarcomas enable clinically meaningful screening of multiple drugs and combinations, marking a significant advance in personalized care for these high-risk diseases.

Enzymatic modification of cotton fibre polysaccharides as an enabler of sustainable laundry detergents.

Cotton is the most common natural fibre used in textile manufacture, used alone or with other fibres to create a wide range of fashion clothing and household textiles. Most of these textiles are cleaned using detergents and domestic or commercial washing machines using processes that require many chemicals and large quantities of water and energy. Enzymes can reduce this environmental footprint by enabling effective detergency at reduced temperatures, mostly by directly attacking substrates present in the soils.

Approach and withdrawal from cognitively effortful activities: Development, validation, and transdiagnostic clinical utility of a cognitive motivation scale.

Background: Deficits in cognition and motivation predict functioning in depressive and psychotic disorders. However, experimental tasks of cognitive motivation are inconsistently correlated with functioning, time-intensive, and not intuitive in clinical practice. We aimed to develop and validate a self-report instrument to assess motivation processes pertinent to engagement with cognitive activities in daily life.

The modified RNA base acpU is an attachment site for N-glycans in glycoRNA.

GlycoRNA consists of RNAs modified with secretory N-glycans that are presented on the cell surface. Although previous work supported a covalent linkage between RNA and glycans, the direct chemical nature of the RNA-glycan connection was not described. Here, we develop a sensitive and scalable protocol to detect and characterize native glycoRNAs.

Targeting thalamocortical circuits for closed-loop stimulation in Lennox-Gastaut syndrome.

This paper outlines the therapeutic rationale and neurosurgical targeting technique for bilateral, closed-loop, thalamocortical stimulation in Lennox-Gastaut syndrome, a severe form of childhood-onset epilepsy. Thalamic stimulation can be an effective treatment for Lennox-Gastaut syndrome, but complete seizure control is rarely achieved. Outcomes may be improved by stimulating areas beyond the thalamus, including cortex, but the optimal targets are unknown.

Cancer-stromal cell interactions in breast cancer brain metastases induce glycocalyx-mediated resistance to HER2-targeting therapies.

Brain metastatic breast cancer is particularly lethal largely due to therapeutic resistance. Almost half of the patients with metastatic HER2-positive breast cancer develop brain metastases, representing a major clinical challenge. We previously described that cancer-associated fibroblasts are an important source of resistance in primary tumors.

Angiogenic Gene Therapy for Refractory Angina: Results of the EXACT Phase 2 Trial.

Background: XC001 is a novel adenoviral-5 vector designed to express multiple isoforms of VEGF (vascular endothelial growth factor) and more safely and potently induce angiogenesis. The EXACT trial (Epicardial Delivery of XC001 Gene Therapy for Refractory Angina Coronary Treatment) assessed the safety and preliminary efficacy of XC001 in patients with no option refractory angina.

Methods: In this single-arm, multicenter, open-label trial, 32 patients with no option refractory angina received a single treatment of XC001 (1×10 viral particles) via transepicardial delivery.

Glutamate Signaling in Patients With Parkinson Disease With REM Sleep Behavior Disorder.

Background And Objectives: Clinical heterogeneity of patients with Parkinson disease (PD) is well recognized. PD with REM sleep behavior disorder (RBD) is a more malignant phenotype with faster motor progression and higher nonmotor symptom burden. However, the neural mechanisms underlying this clinical divergence concerning imbalances in neurotransmitter systems remain elusive.

Directed evolution of genetically encoded LYTACs for cell-mediated delivery.

Lysosome-targeting chimeras (LYTACs) are a promising therapeutic modality to drive the degradation of extracellular proteins. However, early versions of LYTAC contain synthetic glycopeptides that cannot be genetically encoded. Here, we present our designs for a fully genetically encodable LYTAC (GELYTAC), making our tool compatible with integration into therapeutic cells for targeted delivery at diseased sites.

Reductions in remnant cholesterol and VLDL cholesterol through inhibition of ANGPTL3 protein synthesis: an analysis from the TRANSLATE-TIMI 70 trial.

Aims: Remnant cholesterol and very low-density lipoprotein cholesterol (VLDL-C) are increasingly recognized risk factors for atherosclerotic disease with few therapeutic options. Angiopoietin-like 3 (ANGPTL3), a key protein in the metabolism of triglyceride-rich lipoproteins, is a promising target.

Methods And Results: TRANSLATE-TIMI 70 was a double-blind, placebo-controlled randomized trial testing seven dose regimens of vupanorsen, an antisense oligonucleotide against ANGPTL3, in adults with non-HDL-C ≥ 100 mg/dL and triglycerides 150-500 mg/dL.

EMPOWER: A Multi-Site Pilot Trial to Reduce Distress in Surrogate Decision-Makers in the ICU.

Context: Efforts to reduce the psychological distress of surrogate decision-makers of critically ill patients have had limited success, and some have even exacerbated distress.

Objectives: The aim of this study was to determine the feasibility, acceptability, and preliminary efficacy of EMPOWER (Enhancing and Mobilizing the POtential for Wellness and Resilience), an ultra-brief (∼2-hour), 6-module manualized psychological intervention for surrogates.

Methods: Surrogates who reported significant anxiety and/or an emotionally close relationship with the patient (n=60) were randomized to receive EMPOWER or enhanced usual care (EUC) at one of three metropolitan hospitals.

Bioorthogonal Metabolic Labeling of the Virulence Factor Phenolic Glycolipid in Mycobacteria.

Surface lipids on pathogenic mycobacteria modulate infection outcomes by regulating host immune responses. Phenolic glycolipid (PGL) is a host-modulating surface lipid that varies among clinical strains. PGL is also found in , where it promotes infection of zebrafish through effects on the innate immune system.

Binocular Home Treatment for Amblyopia: Gains Stable for One Year.

Purpose: To report the long-term outcomes of a noninferiority randomized controlled trial (RCT) with a binocular eye-tracking-based home treatment (CureSight; NovaSight, Ltd.) in patients with amblyopia.

Design: Prospective, multicenter, nonrandomized, long-term follow-up observational study of an RCT.