Cholesterol Accumulation Promotes Photoreceptor Senescence and Retinal Degeneration.

Purpose: Dysregulated cholesterol metabolism is critical in the pathogenesis of AMD. Cellular senescence contributes to the development of numerous age-associated diseases. In this study, we investigated the link between cholesterol burden and the cellular senescence of photoreceptors.

RETRACTION: Exosomal miR-106a-5p Accelerates the Progression of Nasopharyngeal Carcinoma Through FBXW7-Mediated TRIM24 Degradation.

C.-W. Li, J.

CT1812 biomarker signature from a meta-analysis of CSF proteomic findings from two Phase 2 clinical trials in Alzheimer's disease.

Introduction: CT1812 is in clinical development for the treatment of Alzheimer's disease (AD). Cerebrospinal fluid (CSF) exploratory proteomics was employed to identify pharmacodynamic biomarkers of CT1812 in mild to moderate AD from two independent clinical trials.

Methods: Unbiased analysis of tandem-mass tag mass spectrometry (TMT-MS) quantitative proteomics, pathway analysis and correlation analyses with volumetric magnetic resonance imaging (vMRI) were performed for the SPARC cohort (NCT03493282).

Modeling of HIV-1 prophylactic efficacy and toxicity with islatravir shows non-superiority for oral dosing, but promise as a subcutaneous implant.

HIV prevention with pre-exposure prophylaxis (PrEP) constitutes a major pillar in fighting the ongoing epidemic. While daily oral PrEP adherence may be challenging, long-acting (LA-)PrEP in oral or implant formulations could overcome frequent dosing with convenient administration. The novel drug islatravir (ISL) may be suitable for LA-PrEP, but dose-dependent reductions in T cell and lymphocyte counts were observed at high doses.

An explainable language model for antibody specificity prediction using curated influenza hemagglutinin antibodies.

Despite decades of antibody research, it remains challenging to predict the specificity of an antibody solely based on its sequence. Two major obstacles are the lack of appropriate models and the inaccessibility of datasets for model training. In this study, we curated >5,000 influenza hemagglutinin (HA) antibodies by mining research publications and patents, which revealed many distinct sequence features between antibodies to HA head and stem domains.

Acute Bony Bankart Injury With Glenoid Rim Fracture Treated by Arthroscopic Bankart Repair.

A bony Bankart lesion is a torn labrocapsular complex with a glenoid rim fracture. In this case report, a patient with an acute bony Bankart injury presented with severe shoulder pain and limited range of motion following a road traffic accident. The injury was diagnosed through imaging studies and required arthroscopic bony Bankart repair.

Host-parasitoid trophic webs in complex agricultural systems.

The composition and dynamics of ecological communities are complex because of the presence of large numbers of organisms, belonging to many different species, each with their own evolutionary history, and their numerous interactions. The construction and analysis of trophic webs summarize interactions across trophic levels and link community structure to properties such as ecosystem services. We focus on agroecological communities, which may be simpler than natural communities but nonetheless present considerable challenges to describe and understand.

Mechanistic insights into a heterobifunctional degrader-induced PTPN2/N1 complex.

PTPN2 (protein tyrosine phosphatase non-receptor type 2, or TC-PTP) and PTPN1 are attractive immuno-oncology targets, with the deletion of Ptpn1 and Ptpn2 improving response to immunotherapy in disease models. Targeted protein degradation has emerged as a promising approach to drug challenging targets including phosphatases. We developed potent PTPN2/N1 dual heterobifunctional degraders (Cmpd-1 and Cmpd-2) which facilitate efficient complex assembly with E3 ubiquitin ligase CRL4, and mediate potent PTPN2/N1 degradation in cells and mice.

Evaluation of a point-of-care rapid HIV antibody test with insights into acute HIV symptomatology in a population with low prevalence.

Many emergency departments (ED) use rapid human immunodeficiency virus (HIV) antibody tests as screening tools, despite limited sensitivity for detecting acute HIV infections. In a 4-year retrospective analysis of 1,192 patients, we evaluated the performance of a third-generation rapid HIV antibody assay tested at point-of-care (POC, Chembio Sure Check HIV 1/2) against in-lab fourth-generation screening (Abbott Architect Ag/Ab Combo). Compared to complete algorithmic testing, the POC test demonstrated a 92.

Acute Aortic Dissection: Observational Lessons Learned From 11 000 Patients.

Background: Over the past 25 years, diagnosis and therapy for acute aortic dissection (AAD) have evolved. We aimed to study the effects of these iterative changes in care.

Methods: Patients with nontraumatic AAD enrolled in the International Registry of Acute Aortic Dissection (61 centers; 15 countries) were divided into time-based tertiles (groups) from 1996 to 2022.

Effects of Dapagliflozin in Patients with Membranous Nephropathy.

Introduction: Despite the provision of renin-angiotensin-aldosterone-system inhibitors and immunosuppressive therapies, membranous nephropathy often progresses to end-stage kidney disease (ESKD). The objective of this prespecified analysis was to assess the safety and efficacy of dapagliflozin in patients with membranous nephropathy enrolled in the DAPA-CKD trial.

Methods: Patients with an estimated glomerular filtration rate (eGFR) of 25-75 mL/min/1.

Cardiac intravoxel incoherent motion diffusion-weighted imaging to assess myocardial microcirculation dysfunction in hypertension.

Background: Myocardial microcirculation dysfunction is the most potent predictor of adverse cardiovascular events in hypertension. The current study aimed to apply intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) to assess hypertension-related microcirculation dysfunction.

Methods: In this prospective study, 102 participants were recruited from our hospital and underwent cardiac magnetic resonance (CMR) examination on a 3T scanning system.

Standardized wireless deep brain stimulation system for mice.

Deep brain stimulation (DBS) has emerged as a revolutionary technique for accessing and modulating brain circuits. DBS is used to treat dysfunctional neuronal circuits in neurological and psychiatric disorders. Despite over two decades of clinical application, the fundamental mechanisms underlying DBS are still not well understood.

Fractures by race and ethnicity in a diverse sample of postmenopausal women: a current evaluation among Hispanic and Asian origin groups.

Using 1998-2022 Women's Health Initiative (WHI) data, our study provides contemporary fracture data by race and ethnicity, specifically focusing on Hispanic and Asian women. Fractures of interest included any clinical, hip, and major osteoporotic fractures (MOFs). We utilized the updated race and ethnicity information collected in 2003, which included seven Asian and five Hispanic origin groups.

Discovery of VU6008677: A Structurally Distinct Tricyclic M Positive Allosteric Modulator with Improved CYP450 Profile.

This Letter details our efforts to develop novel tricyclic muscarinic acetylcholine receptor subtype 4 (M) positive allosteric modulator (PAM) scaffolds with improved pharmacological properties. This endeavor involved a "tie-back" strategy to replace the 3-amino-5-chloro-4,6-dimethylthieno[2,3-]pyridine-2-carboxamide core, which led to the discovery of two novel tricyclic cores: an 8-chloro-9-methylpyrido[3',2':4,5]thieno[3,2-]pyrimidin-4-amine core and 8-chloro-7,9-dimethylpyrido[3',2':4,5]furo[3,2-]pyrimidin-4-amine core. Both tricyclic cores displayed low nanomolar potency against human M and greatly reduced cytochrome P450 inhibition when compared with parent compound .

Reduction in kidney function decline and risk of severe clinical events in agalsidase beta-treated Fabry disease patients: a matched analysis from the Fabry Registry.

Background: Patients with Fabry disease (FD, α-galactosidase A deficiency or absence) accumulate glycosphingolipids, leading to progressive dysfunction of kidneys, heart and nervous system. Generalizable real-world outcomes following agalsidase beta treatment initiation outside trials are limited. We investigated the associations of long-term agalsidase beta treatment with estimated glomerular filtration rate (eGFR) changes over time and the risk of developing a composite clinical event in a matched analysis of treated and untreated patients with FD.

Anaemia and quality of life in chronic kidney disease: a consensus document from the European Anaemia of CKD Alliance.

Anaemia is common in chronic kidney disease (CKD) and has a significant impact on quality of life (QoL), work productivity and outcomes. Current management includes oral or intravenous iron and erythropoiesis-stimulating agents (ESAs), to which hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) have been recently added, increasing the available therapeutic options. In randomised controlled trials, only intravenous iron improved cardiovascular outcome, while some ESAs were associated with increased adverse cardiovascular events.

Performance of amide proton transfer imaging to differentiate true progression from therapy-related changes in gliomas and metastases.

Objectives: Differentiating true progression or recurrence (TP/TR) from therapy-related changes (TRC) is complex in brain tumours. Amide proton transfer-weighted (APT) imaging is a chemical exchange saturation transfer (CEST) MRI technique that may improve diagnostic accuracy during radiological follow-up. This systematic review and meta-analysis elucidated the level of evidence and details of state-of-the-art imaging for APT-CEST in glioma and brain metastasis surveillance.