Preclinical and Clinical Pharmacokinetics of a New Preservative-Free Bimatoprost 0.01% Ophthalmic Gel to Treat Glaucoma and Ocular Hypertension.

Pharmacokinetic evaluation of ocular penetration and systemic accumulation of preservative-free bimatoprost 0.01% ophthalmic gel (PFB 0.01% gel).

scMaui: a widely applicable deep learning framework for single-cell multiomics integration in the presence of batch effects and missing data.

The recent advances in high-throughput single-cell sequencing have created an urgent demand for computational models which can address the high complexity of single-cell multiomics data. Meticulous single-cell multiomics integration models are required to avoid biases towards a specific modality and overcome sparsity. Batch effects obfuscating biological signals must also be taken into account.

Additional Guidance on the Use of the PRESERFLO™ MicroShunt in the Treatment of Glaucoma: Insights from a Second Delphi Consensus Panel.

Introduction: The PRESERFLO™ MicroShunt (PMS) has been proven to significantly lower intraocular pressure (IOP) in patients with glaucoma and has been available for use since 2019. With increasing published evidence and growing experience of glaucoma surgeons, the aim of this modified Delphi panel was to build on the findings of a previous Delphi panel conducted in 2021 and provide further guidance on the role of the PMS to treat patients with glaucoma in Europe.

Methods: Thirteen European glaucoma surgeons experienced in the PMS procedure participated in a 3-round modified Delphi panel.

Preservative-Free Bimatoprost 0.01% Ophthalmic Gel for Glaucoma Therapy: A Phase III Randomized Controlled Trial.

Prcis: Noninferiority of efficacy was demonstrated for a preservative-free bimatoprost 0.01% compared with BAK-containing bimatoprost 0.01% following a 12-week treatment period in patients with open angle glaucoma or ocular hypertension.

FAST® questionnaire for identifying glaucoma patients at risk for ocular surface disease.

Objectives: To evaluate the validity and reliability of the new Fast Assessment of the Ocular Surface Trouble (FAST®) questionnaire for identifying glaucoma or ocular hypertension (OHT) patients at risk of ocular surface disease (OSD).

Methods: A multicenter, international, cross-sectional, epidemiological survey evaluated the most accurate interview items and ocular signs on the initial 14-item version of FAST® to develop a shorter version for routine, quick clinical use. Rasch analysis and least absolute shrinkage and selection operator (LASSO) method was used to reduce the number of items on the questionnaire.

European Glaucoma Society - A guide on surgical innovation for glaucoma.

PROLOGUE:

Testing and Practical Implementation of a User-Friendly Personalized and Long-Term Electronic Informed Consent Prototype in Clinical Research: Mixed Methods Study.

Background: Over the years, there has been increasing interest in electronic informed consent (eIC) in clinical research. The user-friendliness of an eIC application and its acceptance by stakeholders plays a central role in achieving successful implementation.

Objective: This study aims to identify insights for the design and implementation of a user-friendly, personalized, and long-term eIC application based on a usability study with (potential) research participants and semistructured interviews with stakeholders on the practical integration of such an application into their daily practice.

Clinical impact of the genomic landscape and leukemogenic trajectories in non-intensively treated elderly acute myeloid leukemia patients.

To characterize the genomic landscape and leukemogenic pathways of older, newly diagnosed, non-intensively treated patients with AML and to study the clinical implications, comprehensive genetics analyses were performed including targeted DNA sequencing of 263 genes in 604 patients treated in a prospective Phase III clinical trial. Leukemic trajectories were delineated using oncogenetic tree modeling and hierarchical clustering, and prognostic groups were derived from multivariable Cox regression models. Clonal hematopoiesis-related genes (ASXL1, TET2, SRSF2, DNMT3A) were most frequently mutated.

Heterogeneity in the gene regulatory landscape of leiomyosarcoma.

Characterizing inter-tumor heterogeneity is crucial for selecting suitable cancer therapy, as the presence of diverse molecular subgroups of patients can be associated with disease outcome or response to treatment. While cancer subtypes are often characterized by differences in gene expression, the mechanisms driving these differences are generally unknown. We set out to model the regulatory mechanisms driving sarcoma heterogeneity based on patient-specific, genome-wide gene regulatory networks.

The GAPDH redox switch safeguards reductive capacity and enables survival of stressed tumour cells.

Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) is known to contain an active-site cysteine residue undergoing oxidation in response to hydrogen peroxide, leading to rapid inactivation of the enzyme. Here we show that human and mouse cells expressing a GAPDH mutant lacking this redox switch retain catalytic activity but are unable to stimulate the oxidative pentose phosphate pathway and enhance their reductive capacity. Specifically, we find that anchorage-independent growth of cells and spheroids is limited by an elevation of endogenous peroxide levels and is largely dependent on a functional GAPDH redox switch.

A randomized clinical trial comparing three fixed combinations of bimatoprost with timolol in patients with open-angle glaucoma or ocular hypertension.

Objective: To compare the efficacy and safety of two fixed combination, preservative-free eye drops (bimatoprost 0.01% in combination with either timolol 0.1% or 0.

Expert Consensus on the Use of the PRESERFLO™ MicroShunt Device in the Treatment of Glaucoma: A Modified Delphi Panel.

Introduction: The implantation of the PRESERFLO™ MicroShunt (PMS) device has been shown to significantly lower increased intraocular pressure (IOP) in patients with primary open-angle glaucoma (POAG). However, guidelines on best practice for patient selection and pre-/peri-/postoperative care management are lacking. The aim of this modified Delphi panel was to achieve expert consensus on the role of the PMS to treat patients with glaucoma in Europe.

Load Monitoring Practice in European Elite Football and the Impact of Club Culture and Financial Resources.

Load monitoring is considered important to manage the physical training process in team sports such as Association Football. Previous studies have described the load monitoring practices of elite English football clubs and clubs with an established sports-science department. An examination of a broader international sample is currently not available.

Validation of a high-fidelity training model for fetoscopic spina bifida surgery.

Open fetal surgery for spina bifida (SB) is safe and effective yet invasive. The growing interest in fetoscopic SB repair (fSB-repair) prompts the need for appropriate training. We aimed to develop and validate a high-fidelity training model for fSB-repair.

Missing Self-Induced Activation of NK Cells Combines with Non-Complement-Fixing Donor-Specific Antibodies to Accelerate Kidney Transplant Loss in Chronic Antibody-Mediated Rejection.

Background: Binding of donor-specific antibodies (DSAs) to kidney allograft endothelial cells that does not activate the classic complement cascade can trigger the recruitment of innate immune effectors, including NK cells. Activated NK cells contribute to microvascular inflammation leading to chronic antibody-mediated rejection (AMR). Recipient NK cells can also trigger antibody-independent microvascular inflammation by sensing the absence of self HLA class I molecules ("missing self") on allograft endothelial cells.

Smell, an Underrated Early Biomarker for Brain Aging.

Olfaction is in addition to touch the most ancient of our senses, developing already in the womb it decays progressively from 65 years of age with a more pronounced impairment associated with dementia. Despite its clinical relevance and testing accessibility, smell remains an overlooked biomarker, which is rarely used by neurologists in the early screening phase. In this perspective article, we outline the reasons underlying the lack of awareness for this sense.

Embolic strokes of undetermined source: theoretical construct or useful clinical tool?

In 2014, the definition of embolic strokes of undetermined source (ESUS) emerged as a new clinical construct to characterize cryptogenic stroke (CS) patients with complete vascular workup to determine nonlacunar, nonatherosclerotic strokes of presumable embolic origin. NAVIGATE ESUS, the first phase III randomized-controlled, clinical trial (RCT) comparing rivaroxaban (15 mg daily) with aspirin (100 mg daily), was prematurely terminated for lack of efficacy after enrollment of 7213 patients. Except for the lack of efficacy in the primary outcome, rivaroxaban was associated with increased risk of major bleeding and hemorrhagic stroke compared with aspirin.

Lack of an Association between a Polymorphism in the KRAS 3' Untranslated Region (rs61764370) and Endometriosis in a Large European Case-Control Study.

Background: Endometriosis is a common disorder that affects 6-10% of reproductive age women. In a previous study, we demonstrated that a polymorphism in let-7 microRNA-binding site in the 3' untranslated region of the KRAS gene was found in 31% of subjects with endometriosis resistant to medical therapy. This polymorphism was now tested in a large, case-control study.

Alberta Stroke Program Early CT Score Versus Computed Tomographic Perfusion to Predict Functional Outcome After Successful Reperfusion in Acute Ischemic Stroke.

Background and Purpose- We aimed to compare the ability of conventional Alberta Stroke Program Early CT Score (ASPECTS), automated ASPECTS, and ischemic core volume on computed tomographic perfusion to predict clinical outcome in ischemic stroke because of large vessel occlusion ≤18 hours after symptom onset. Methods- We selected patients with acute ischemic stroke from the CRISP study (Computed Tomographic Perfusion to Predict Response to Recanalization in Ischemic Stroke Project) with successful reperfusion (modified treatment in cerebral ischemia score 2b or 3). We used e-ASPECTS software to calculate automated ASPECTS and RAPID software to estimate ischemic core volumes.

Endometriosis is associated with aberrant metabolite profiles in plasma.

Objective: To identify metabolites that are associated with and predict the presence of endometriosis.

Design: Metabolomics study using state-of-the-art mass spectrometry approaches.

Setting: University hospital and universities.