Understanding recent advances in non-amyloid/non-tau (NANT) biomarkers and therapeutic targets in Alzheimer's disease.

Unlabelled: The Alzheimer's disease (AD) research community continues to make great strides in expanding approaches for early detection and treatment of the disease, including recent advances in our understanding of fundamental AD pathophysiology beyond the classical targets: beta-amyloid and tau. Recent clinical trial readouts implicate a variety of non-amyloid/non-tau (NANT) approaches that show promise in slowing cognitive decline for people with AD. The Alzheimer's Association Research Roundtable (AARR) meeting held on December 13-14, 2022, reviewed the current state of NANT targets on underlying AD pathophysiology and their contribution to cognitive decline, the current data on a diverse range of NANT biomarkers and therapeutic targets, and the integration of NANT concepts in clinical trial designs.

Hyperactive delta isoform of PI3Kinase enables long distance regeneration of adult rat corticospinal tract.

Neurons in the central nervous system (CNS) lose regenerative potential with maturity, leading to minimal corticospinal tract (CST) axon regrowth after spinal cord injury (SCI). In young rodents, knockdown of PTEN, which antagonises PI3K signalling by hydrolysing PIP3, promotes axon regeneration following SCI. However, this effect diminishes in adults, potentially due to lower PI3K activation leading to reduced PIP3.

Synergistic design of CuO/CoFe₂O₄/MWCNTs ternary nanocomposite for enhanced photocatalytic degradation of tetracycline under visible light.

This study involves a novel CuO/CoFe₂O₄/MWCNTs (CCT) nanocomposite, developed by integrating cobalt ferrite (CoFe₂O₄) and copper oxide (CuO) nanoparticles onto multi-walled carbon nanotubes (MWCNTs), for the degradation of tetracycline (TC) under visible light. The photocatalyst was extensively characterized using XRD, HR-SEM, EDX, HR-TEM, UV-Vis, BET, and PL analysis. The synthesized CoFe₂O₄ and CuO nanoparticles exhibited crystallite sizes of 46.

One-year mortality and re-admission rate by disease etiology in National Heart Failure Registry of India.

Survival outcomes of patients with heart failure (HF) based on their disease etiology are not well described. Here, we provide one-year mortality outcomes of 10850 patients with HF (mean age = 59.9 years, 31% women) in India.

Machine learning derived retinal pigment score from ophthalmic imaging shows ethnicity is not biology.

Few metrics exist to describe phenotypic diversity within ophthalmic imaging datasets, with researchers often using ethnicity as a surrogate marker for biological variability. We derived a continuous, measured metric, the retinal pigment score (RPS), that quantifies the degree of pigmentation from a colour fundus photograph of the eye. RPS was validated using two large epidemiological studies with demographic and genetic data (UK Biobank and EPIC-Norfolk Study) and reproduced in a Tanzanian, an Australian, and a Chinese dataset.

Infrared nanosensors of piconewton to micronewton forces.

Mechanical force is an essential feature for many physical and biological processes, and remote measurement of mechanical signals with high sensitivity and spatial resolution is needed for diverse applications, including robotics, biophysics, energy storage and medicine. Nanoscale luminescent force sensors excel at measuring piconewton forces, whereas larger sensors have proven powerful in probing micronewton forces. However, large gaps remain in the force magnitudes that can be probed remotely from subsurface or interfacial sites, and no individual, non-invasive sensor is capable of measuring over the large dynamic range needed to understand many systems.

Phenotyping atherosclerotic plaque and perivascular adipose tissue: signalling pathways and clinical biomarkers in atherosclerosis.

Computed tomography coronary angiography provides a non-invasive evaluation of coronary artery disease that includes phenotyping of atherosclerotic plaques and the surrounding perivascular adipose tissue (PVAT). Image analysis techniques have been developed to quantify atherosclerotic plaque burden and morphology as well as the associated PVAT attenuation, and emerging radiomic approaches can add further contextual information. PVAT attenuation might provide a novel measure of vascular health that could be indicative of the pathogenetic processes implicated in atherosclerosis such as inflammation, fibrosis or increased vascularity.

Minimum 10-Year Clinical and Functional Outcomes, and Return to Sport After Sternoclavicular Joint Reconstruction for Sternoclavicular Joint Instability.

Background: Sternoclavicular joint (SCJ) instability can lead to pain, reduced function, and an inability to perform sports and activities of daily living. Reconstruction of the SCJ using hamstring autograft in a figure-of-8 configuration has demonstrated good outcomes at short- and midterm follow-ups, but there is a paucity of literature on long-term outcomes.

Purpose: To evaluate the long-term clinical and functional outcomes after SCJ reconstruction, with a focus on return to sport, instability recurrence, and revision surgery.

In Search of Candidate Protein Biomarkers Related to COVID-19 in Solid Tissues and Non-Blood Fluids: An Update.

Purpose: During COVID-19, significant changes in protein abundance can be linked with disease-related processes. The mass spectrometry-based proteomics of COVID-19-related biomarkers can help with the prognosis and diagnosis of this severe disease.

Design: Here, we surveyed scientific works in terms of proteomic analysis of solid tissues and non-blood fluids from COVID-19 patients.

Long-Term Risk of Acute Myocardial Infarction in Patients With a Transient Ischemic Attack: A Danish Nationwide Cohort Study.

Background: Sparse information regarding the long-term risk of acute myocardial infarction (MI) following a transient ischemic attack (TIA) emphasizes further research to guide preventive strategies and risk stratification in patients with a TIA.

Methods: We conducted a nationwide cohort study to investigate the 5-year risk of MI and all-cause mortality in patients with a first-time TIA. Patients with a first-time TIA were identified in the Danish Stroke Registry (2013-2020), matched on age, sex, and calendar year (1:4) with the general population and (1:1) with patients with first-time ischemic stroke.

Modification of Fc-fusion protein structures to enhance efficacy of cancer vaccine in plant expression system.

Epithelial cell adhesion molecule (EpCAM) fused to IgG, IgA and IgM Fc domains was expressed to create IgG, IgA and IgM-like structures as anti-cancer vaccines in Nicotiana tabacum. High-mannose glycan structures were generated by adding a C-terminal endoplasmic reticulum (ER) retention motif (KDEL) to the Fc domain (FcK) to produce EpCAM-Fc and EpCAM-FcK proteins in transgenic plants via Agrobacterium-mediated transformation. Cross-fertilization of EpCAM-Fc (FcK) transgenic plants with Joining chain (J-chain, J and JK) transgenic plants led to stable expression of large quaternary EpCAM-IgA Fc (EpCAM-A) and IgM-like (EpCAM-M) proteins.

A Pooled Pharmacokinetic Analysis for Piperacillin/Tazobactam Across Different Patient Populations: From Premature Infants to the Elderly.

Background And Objectives: The pharmacokinetics (PK) of piperacillin/tazobactam (PIP/TAZ) is highly variable across different patient populations and there are controversies regarding non-linear elimination as well as the fraction unbound of PIP (f). This has led to a plethora of subgroup-specific models, increasing the risk of misusing published models when optimising dosing regimens. In this study, we aimed to develop a single model to simultaneously describe the PK of PIP/TAZ in diverse patient populations and evaluate the current dosing recommendations by predicting the PK/pharmacodynamics (PD) target attainment throughout life.

Extracellular vesicles from platelet-poor plasma possess anti-inflammatory and anti-catabolic effects in chondrocytes stimulated with IL-1β or synovial membrane-conditioned media.

Background: Although osteoarthritis (OA) is the most prevalent form of arthritis, there is still no effective treatment capable of combining immunomodulatory effects with cartilage repair. Extracellular vesicles (EVs) represent a promising new generation of cell-free therapies for OA. Blood-derived products, including plasma, are an easily available and abundant source of EVs with anti-inflammatory and regenerative properties.

Somatic PTEN and ARID1A loss and endometriosis disease burden: a longitudinal study.

Study Question: Is there an association between the somatic loss of PTEN (phosphatase and tensin homolog) and ARID1A (AT-rich interaction domain 1A) and endometriosis disease severity and worse clinical outcomes?

Summary Answer: Somatic PTEN loss in endometriosis epithelium was associated with greater disease burden and subsequent surgical complexity.

What Is Known Already: Somatic cancer-driver mutations including those involving the PTEN and ARID1A genes exist in endometriosis without cancer; however, their clinical impact remains unclear.

Study Design, Size, Duration: This prospective longitudinal study involved endometriosis tissue and clinical data from 126 participants who underwent surgery at a tertiary center for endometriosis (2013-2017), with a follow-up period of 5-9 years.

Lead Phytomolecules for Treating Parkinson's Disease.

One percent of persons over 65 years of age suffer from Parkinson's disease, a neurological ailment marked by dopaminergic neurons in the nigrostriatal pathway gradually dying and being depleted in the striatum. Parkin and PINK1 gene mutations, which are essential for mitophagy and impair mitochondrial function, are the cause of it. Parkinson's disease is linked to a number of motor and impairment disorders, including bradykinesia, rigid muscles, tremor at rest, and imbalance.

Exploring Anisotropy Contributions in Mn Co FeO Ferrite Nanoparticles for Biomedical Applications.

Designing well-defined magnetic nanomaterials is crucial for various applications, and it demands a comprehensive understanding of their magnetic properties at the microscopic level. In this study, we investigate the contributions to the total anisotropy of Mn/Co mixed spinel nanoparticles. By employing neutron measurements sensitive to the spatially resolved surface anisotropy with sub-Å space resolution, we reveal an additional contribution to the anisotropy constant arising from shape anisotropy and interparticle interactions.

Clinical and Biomarker Determinants for Recurrent Stroke in Patients With Atrial Fibrillation: A Systematic Review and Meta-Analysis.

Background And Objectives: Despite effective secondary prevention, including oral anticoagulant (OAC) therapy, the risk of recurrent stroke (RS) in patients with atrial fibrillation (AF) remains substantial with an annualized risk of 3.2%-6.5% per year.

Discovery of 4-(5-Membered)Heteroarylether-6-methylpicolinamide Negative Allosteric Modulators of Metabotropic Glutamate Receptor Subtype 5.

This Letter details our efforts to develop novel, non-acetylene-containing metabotropic glutamate receptor subtype 5 (mGlu) negative allosteric modulators (NAMs) with improved pharmacological properties. This endeavor involved replacing the ether-linked pyrimidine moiety, a metabolic liability, with various 5-membered heterocycles. From this exercise, we identified , a highly brain penetrant and selective mGlu NAM which displayed moderate potency against both human and rat mGlu.

High stability of the radical at the catalytic center of cytochrome c oxidase.

In aerobic organisms, cellular respiration is associated with electron transfer through a respiratory system of membrane-bound complexes. This electron flow is terminated by the reduction of dioxygen to water by respiratory oxidases. Cytochrome c oxidase (CcO) is a widely distributed heme-copper-oxygen reductase (HCO) found in all mitochondria and some bacteria.

Long-term dupilumab efficacy in type 2 asthma regardless of baseline characteristics.

https://bit.ly/3XSwX62.

T cell margination: investigating the detour of T cells following forimtamig treatment in humanized mice.

T cell bispecific antibodies (TCBs) are a promising new class of therapeutics for relapsed/refractory multiple myeloma. A frequently observed, yet incompletely understood effect of this treatment is the transient reduction of circulating T cell counts, also known as T cell margination (TCM). After administration of the GPRC5D-targeting TCB forimtamig (RG6234), TCM occurred in patients and correlated with cytokine release and soluble B cell maturation antigen decrease.

Late Bedtime from the Perspective of Adolescents: A Qualitative Study.

Purpose: Later sleep timing is a key determinant of reduced sleep duration and quality in adolescents and is associated with negative mental and physical outcomes. However, little is known about adolescents' views on late bedtime. The study's purpose is to explore adolescents' perspectives on why they go to sleep late during school nights and what would help them to go to bed earlier.