N-Pep-12 Improves Hippocampal Cognitive Function and Increases Neuroplasticity and Neurogenesis Markers.

This study investigates the effects of N‑PEP‑12, a neuroprotective dietary supplement, on cognitive function, neuroplasticity, and neurogenesis in aged 129S1/SvImJ (S1) mice, which are known for age‑associated cognitive impairments. The primary objective was to determine whether N‑PEP‑12 could improve memory retention and enhance neural health by modulating hippocampal plasticity and neurogenesis. S1 mice were chronically treated with N‑PEP‑12 or a Vehicle to assess its impact on cognitive performance using cued fear conditioning (CFC) and object location memory (OLM) tests.

Circulating metabolite signatures indicate differential gut-liver crosstalk in lean and obese MASLD.

BACKGROUNDAlterations in circulating metabolites have been described in obese metabolic dysfunction-associated steatotic liver disease (MASLD), but data on lean MASLD are lacking. We investigated serum metabolites, including microbial bile acids and short-chain fatty acids (SCFAs), and their association with lean and obese MASLD.METHODSSerum samples from 204 people of European descent were allocated to groups: lean healthy, lean MASLD, obese healthy, and obese MASLD (n = 47).

Lessons learned from a candidate gene study investigating aromatase inhibitor treatment outcome in breast cancer.

The role of germline genetics in adjuvant aromatase inhibitor (AI) treatment efficacy in ER-positive breast cancer is poorly understood. We employed a two-stage candidate gene approach to examine associations between survival endpoints and common germline variants in 753 endocrine resistance-related genes. For a discovery cohort, we screened the Breast Cancer Association Consortium database (n ≥ 90,000 cases) and retrieved 2789 AI-treated patients.

N-Pep-Zn Improves Cognitive Functions and Acute Stress Response Affected by Chronic Social Isolation in Aged Spontaneously Hypertensive Rats (SHRs).

Background/objectives: Aging and chronic stress are regarded as the most important risk factors of cognitive decline. Aged spontaneously hypertensive rats (SHRs) represent a suitable model of age-related vascular brain diseases. The aim of this study was to explore the effects of chronic isolation stress in aging SHRs on their cognitive functions and response to acute stress, as well as the influence of the chronic oral intake of N-Pep-Zn, the Zn derivative of N-PEP-12.

A theory of degrees in education.

Degrees are presumably the most important institution in education markets. However, despite their high relevance, degrees and their design features remain poorly understood within the economics of education. This study addresses this gap.

In silico and biological analyses of missense variants of the human biliary efflux transporter ABCC2: effects of novel rare missense variants.

Background And Purpose: The ATP-dependent biliary efflux transporter ABCC2, also known as multidrug resistance protein 2 (MRP2), is essential for the cellular disposition and detoxification of various xenobiotics including drugs as well as endogenous metabolites. Common functionally relevant ABCC2 genetic variants significantly alter drug responses and contribute to side effects. The aim of this study was to determine functional consequences of rare variants identified in subjects with European ancestry using in silico tools and in vitro analyses.

A leadless ventricular pacemaker providing atrioventricular synchronous pacing in the real-world setting: 12-Month results from the Micra AV post-approval registry.

Background: Advances in leadless pacemaker technology have enabled accelerometer-based atrioventricular (AV) synchronous pacing by sensing atrial mechanical contraction.

Objective: The purpose of this study was to report the performance of the Micra AV leadless pacemaker from the worldwide Micra AV post-approval registry (PAR) through 12 months.

Methods: The Micra AV PAR is a prospective, single-arm, observational registry designed to assess the safety and effectiveness of Micra AV in a real-world setting.

A Neurofilament-L reporter cell line for the quantification of early neuronal differentiation: A Bioassay for neurotrophic activities.

Background: Neurotrophic activity constitutes a crucial factor in the recovery from neurological injuries and is impaired in neurodegenerative disorders. Preclinical studies of neurotrophic factors to improve outcome of neurodegenerative diseases have yielded promising results. However, due to the complexity of these therapies, the clinical translation of this approach was so far not successful and more feasible treatments with neurotrophic activity may be promising alternatives.

Novel drug transporter substrates identification: An innovative approach based on metabolomic profiling, in silico ligand screening and biological validation.

Solute carrier (SLC) transport proteins are fundamental for the translocation of endogenous compounds and drugs across membranes, thus playing a critical role in disease susceptibility and drug response. Because only a limited number of transporter substrates are currently known, the function of a large number of SLC transporters is elusive. Here, we describe the proof-of-concept of a novel strategy to identify SLC transporter substrates exemplarily for the proton-coupled peptide transporter (PEPT) 2 (SLC15A2) and multidrug and toxin extrusion (MATE) 1 transporter (SLC47A1), which are important renal transporters of drug reabsorption and excretion, respectively.

Platelet miRNAs: differential expression in coronary artery disease and associations with course of left ventricular systolic function.

Background: MicroRNAs are paramount in post transcriptional gene regulation. We investigated platelet miRNAs in patients with CAD and examined potential associations with course of left ventricular ejection fraction (LVEF%).

Materials And Methods: In a first cohort, 62 MiRNAs were measured in platelets of 100 patients suffering from CAD.

A leadless pacemaker in the real-world setting: Patient profile and performance over time.

Background: While prior Micra trials demonstrated a high implant success rate and favorable safety and efficacy results, changes in implant populations and safety over time is not well studied. The objective of this analysis was to report the performance of Micra in European and Middle Eastern patients and compare to the Micra Investigational Device Exemption (IDE) and Micra Post Approval Registry (PAR) studies.

Methods: The prospective, single-arm Micra Acute Performance European and Middle Eastern (MAP EMEA) registry was designed to further study the performance of Micra in patients from EMEA.

Cross-Ancestry Genome-Wide Association Study Defines the Extended CYP2D6 Locus as the Principal Genetic Determinant of Endoxifen Plasma Concentrations.

The therapeutic efficacy of tamoxifen is predominantly mediated by its active metabolites 4-hydroxy-tamoxifen and endoxifen, whose formation is catalyzed by the polymorphic cytochrome P450 2D6 (CYP2D6). Yet, known CYP2D6 polymorphisms only partially determine metabolite concentrations in vivo. We performed the first cross-ancestry genome-wide association study with well-characterized patients of European, Middle-Eastern, and Asian descent (n = 497) to identify genetic factors impacting active and parent metabolite formation.

From Unit to Dose: A Machine Learning Approach for Precise Prediction of Hemoglobin and Iron Content in Individual Packed Red Blood Cell Units.

Transfusion of packed red blood cells (pRBCs) saves lives, but iron overload limits survival of chronically transfused patients. Quality control methods, which involve entering pRBC units and removing them from the blood supply, reveal that hemoglobin (38.5-79.

Clinical and Experimental Evidence for a Strain-Based Classification of Left Bundle Branch Block-Induced Cardiac Remodeling.

Background: Septal strain patterns measured by echocardiography reflect the severity of left bundle branch block (LBBB)-induced left ventricular (LV) dysfunction. We investigated whether these LBBB strain stages predicted the response to cardiac resynchronization therapy in an observational study and developed a sheep model of LBBB-induced cardiomyopathy.

Methods: The clinical study enrolled cardiac resynchronization therapy patients who underwent echocardiographic examination with speckle-tracking strain analysis before cardiac resynchronization therapy implant.

Development and Implementation of the Data Science Learning Platform for Research Physician.

Data analysis and their application are the unavoidable factors in the activities analyses in health care. Unfortunately, the acquisition of data from large available medical databases is a complex process and requires deep knowledge of computer science and especially knowledge of tools for data management. According to the European General Data Protection Regulation, the problem becomes much more complex.

Untargeted stable isotope-resolved metabolomics to assess the effect of PI3Kβ inhibition on metabolic pathway activities in a PTEN null breast cancer cell line.

The combination of high-resolution LC-MS untargeted metabolomics with stable isotope-resolved tracing is a promising approach for the global exploration of metabolic pathway activities. In our established workflow we combine targeted isotopologue feature extraction with the non-targeted XCMS routine. Metabolites, detected by XCMS as differentially labeled between two biological conditions are subsequently integrated into the original targeted library.

Dendritic Cells or Macrophages? The Microenvironment of Human Clear Cell Renal Cell Carcinoma Imprints a Mosaic Myeloid Subtype Associated with Patient Survival.

Since their initial description by Elie Metchnikoff, phagocytes have sparked interest in a variety of biologic disciplines. These important cells perform central functions in tissue repair and immune activation as well as tolerance. Myeloid cells can be immunoinhibitory, particularly in the tumor microenvironment, where their presence is generally associated with poor patient prognosis.

Modulation of Amyloid-β and Tau in Alzheimer's Disease Plasma Neuronal-Derived Extracellular Vesicles by Cerebrolysin® and Donepezil.

Background: Plasma neuronal-derived extracellular vesicles (NDEV) contain proteins of pathological, diagnostic, and therapeutic relevance.

Objective: We investigated the associations of six plasma NDEV markers with Alzheimer's disease (AD) severity, cognition and functioning, and changes in these biomarkers after Cerebrolysin®, donepezil, and a combination therapy in AD.

Methods: Plasma NDEV levels of Aβ42, total tau, P-T181-tau, P-S393-tau, neurogranin, and REST were determined in: 1) 116 mild to advanced AD patients and in 20 control subjects; 2) 110 AD patients treated with Cerebrolysin®, donepezil, or combination therapy in a randomized clinical trial (RCT).

A novel molecular signature identifies mixed subtypes in renal cell carcinoma with poor prognosis and independent response to immunotherapy.

Background: Renal cell carcinoma (RCC) is a heterogeneous disease comprising histologically defined subtypes. For therapy selection, precise subtype identification and individualized prognosis are mandatory, but currently limited. Our aim was to refine subtyping and outcome prediction across main subtypes, assuming that a tumor is composed of molecular features present in distinct pathological subtypes.

Hepatic Expression of the Na-Taurocholate Cotransporting Polypeptide Is Independent from Genetic Variation.

The hepatic Na-taurocholate cotransporting polypeptide NTCP/ is important for the uptake of bile salts and selected drugs. Its inhibition results in increased systemic bile salt concentrations. NTCP is also the entry receptor for the hepatitis B/D virus.