Exploration of Novel Biomarkers for Neurodegenerative Diseases Using Proteomic Analysis and Ligand-Binding Assays.

Background/objectives: Neurodegenerative diseases are a major cause of morbidity and mortality worldwide, and their public health burden continues to increase. There is an urgent need to develop reliable and sensitive biomarkers to aid the timely diagnosis, disease progression monitoring, and therapeutic development for neurodegenerative disorders. Proteomic screening strategies, including antibody microarrays, are a powerful tool for biomarker discovery, but their findings should be confirmed using quantitative assays.

Artifact Reduction in Interventional Devices Using Virtual Monoenergetic Images and Iterative Metal Artifact Reduction on Photon-Counting Detector CT.

Objectives: The aim of this study was to assess the impact of an iterative metal artifact reduction (iMAR) algorithm combined with virtual monoenergetic images (VMIs) for artifact reduction in photon-counting detector computed tomography (PCDCT) during interventions.

Materials And Methods: Using an abdominal phantom, we conducted evaluations on the efficacy of iMAR and VMIs for mitigating image artifacts during interventions on a PCDCT. Four different puncture devices were employed under 2 scan modes (QuantumSn at 100 kV, Quantumplus at 140 kV) to simulate various clinical scenarios.

The ClinGen Syndromic Disorders Gene Curation Expert Panel: Assessing the Clinical Validity of 111 Gene-Disease Relationships.

Purpose: The Clinical Genome Resource (ClinGen) Gene Curation Expert Panels (GCEPs) have historically focused on specific organ systems or phenotypes; thus, the ClinGen Syndromic Disorders GCEP (SD-GCEP) was formed to address an unmet need.

Methods: The SD-GCEP applied ClinGen's framework to evaluate the clinical validity of genes associated with rare syndromic disorders. 111 Gene-Disease Relationships (GDRs) associated with 100 genes spanning the clinical spectrum of syndromic disorders were curated.

Left Atrial Appendage Closure after Ablation for Atrial Fibrillation.

Background: Oral anticoagulation is recommended after ablation for atrial fibrillation among patients at high risk for stroke. Left atrial appendage closure is a mechanical alternative to anticoagulation, but data regarding its use after atrial fibrillation ablation are lacking.

Methods: We conducted an international randomized trial involving 1600 patients with atrial fibrillation who had an elevated score (≥2 in men and ≥3 in women) on the CHADS-VASc scale (range, 0 to 9, with higher scores indicating a greater risk of stroke) and who underwent catheter ablation.

New insights into the function and molecular mechanisms of Ferredoxin-NADP reductase from Brucella ovis.

Bacterial ferredoxin(flavodoxin)-NADP reductases (FPR) primarily catalyze the transfer of reducing equivalents from NADPH to ferredoxin (or flavodoxin) to provide low potential reducing equivalents for the oxidoreductive metabolism. In addition, they can be implicated in regulating reactive oxygen species levels. Here we assess the functionality of FPR from B.

A critical meta-analysis of predicted no effect concentrations for antimicrobial resistance selection in the environment.

Antimicrobial resistance (AMR) is one of the greatest threats to human health with a growing body of evidence demonstrating that selection for AMR can occur at environmental antimicrobial concentrations. Understanding the concentrations at which selection for resistance may occur is critical to help inform environmental risk assessments and highlight where mitigation strategies are required. A variety of experimental and data approaches have been used to determine these concentrations.

HER2 quantitative continuous scoring for accurate patient selection in HER2 negative trastuzumab deruxtecan treated breast cancer.

Many targeted cancer therapies rely on biomarkers assessed by scoring of immunohistochemically (IHC)-stained tissue, which is subjective, semiquantitative, and does not account for expression heterogeneity. We describe an image analysis-based method for quantitative continuous scoring (QCS) of digital whole-slide images acquired from baseline human epidermal growth factor receptor 2 (HER2) IHC-stained breast cancer tissue. Candidate signatures for patient stratification using QCS of HER2 expression on subcellular compartments were identified, addressing the spatial distribution of tumor cells and tumor-infiltrating lymphocytes.

Tas1R3 Dependent and Independent Recognition of Sugars in the Urethra and the Role of Tuft Cells in this Process.

Increased sugar concentrations on mucosal surfaces display risk factors for infections. This study aims to clarify sugar monitoring in the urethra. Urethral tuft cells (UTC) are known sentinels monitoring the urethral lumen for potentially harmful substances and initiating protective mechanisms.

Multicenter integrated analysis of noncoding CRISPRi screens.

The ENCODE Consortium's efforts to annotate noncoding cis-regulatory elements (CREs) have advanced our understanding of gene regulatory landscapes. Pooled, noncoding CRISPR screens offer a systematic approach to investigate cis-regulatory mechanisms. The ENCODE4 Functional Characterization Centers conducted 108 screens in human cell lines, comprising >540,000 perturbations across 24.

Impact of Comorbid Sleep-Disordered Breathing and Atrial Fibrillation on the Long-Term Outcome After Ischemic Stroke.

Background: Sleep-disordered breathing (SDB) and atrial fibrillation (AF) are highly prevalent in patients with stroke and are recognized as independent risk factors for stroke. Little is known about the impact of comorbid SDB and AF on long-term outcomes after stroke.

Methods: In this prospective cohort study, 353 patients with acute ischemic stroke or transient ischemic attacks were analyzed.

NULISA: a proteomic liquid biopsy platform with attomolar sensitivity and high multiplexing.

The blood proteome holds great promise for precision medicine but poses substantial challenges due to the low abundance of most plasma proteins and the vast dynamic range of the plasma proteome. Here we address these challenges with NUcleic acid Linked Immuno-Sandwich Assay (NULISA™), which improves the sensitivity of traditional proximity ligation assays by ~10,000-fold to attomolar level, by suppressing assay background via a dual capture and release mechanism built into oligonucleotide-conjugated antibodies. Highly multiplexed quantification of both low- and high-abundance proteins spanning a wide dynamic range is achieved by attenuating signals from abundant targets with unconjugated antibodies and next-generation sequencing of barcoded reporter DNA.

Measurement of the Time-Integrated CP Asymmetry in D^{0}→K^{-}K^{+} Decays.

The time-integrated CP asymmetry in the Cabibbo-suppressed decay D^{0}→K^{-}K^{+} is measured using proton-proton collision data, corresponding to an integrated luminosity of 5.7  fb^{-1} collected at a center-of-mass energy of 13 TeV with the LHCb detector. The D^{0} mesons are required to originate from promptly produced D^{*+}→D^{0}π^{+} decays, and the charge of the companion pion is used to determine the flavor of the charm meson at production.

Exploring the Role of Plasma Lipids and Statin Interventions on Multiple Sclerosis Risk and Severity: A Mendelian Randomization Study.

Background And Objectives: There has been considerable interest in statins because of their pleiotropic effects beyond their lipid-lowering properties. Many of these pleiotropic effects are predominantly ascribed to Rho small guanosine triphosphatases (Rho GTPases) proteins. We aimed to genetically investigate the role of lipids and statin interventions on multiple sclerosis (MS) risk and severity.

Calcium scoring on coronary computed angiography tomography with photon-counting detector technology: Predictors of performance.

Introduction: Obtaining accurate coronary artery calcium (CAC) score measurements from CCTA datasets with virtual non-iodine (VNI) algorithms would reduce acquisition time and radiation dose. We aimed to assess the agreement of VNI-derived and conventional true non-contrast (TNC)-based CAC scores and to identify the predictors of accuracy.

Methods: CCTA datasets were acquired with either 120 or 140 ​kVp.

Transcriptomic Maps of Colorectal Liver Metastasis: Machine Learning of Gene Activation Patterns and Epigenetic Trajectories in Support of Precision Medicine.

The molecular mechanisms of the liver metastasis of colorectal cancer (CRLM) remain poorly understood. Here, we applied machine learning and bioinformatics trajectory inference to analyze a gene expression dataset of CRLM. We studied the co-regulation patterns at the gene level, the potential paths of tumor development, their functional context, and their prognostic relevance.

Characteristic 3D foot motion patterns during gait of patients with Charcot-Marie-Tooth identified by cluster analysis.

Background: CMT is a clinically and genetically heterogenous disease with varying degrees of progression. Different foot deformities, gait and movement patterns are observed. In order to achieve an improved, targeted treatment strategy, the participants are divided into characteristic groups using a mathematical cluster analysis based on the data from the three-dimensional foot kinematics during walking.

Effect of Supplementation of Lambs with Whole Cottonseed: Impact on Serum Biomarkers and Infection by Gastrointestinal Parasites under Field Conditions.

The purpose of this trial was to evaluate serum levels of oxidative stress biomarkers and biochemical analytes in crossbred lambs during the rearing phase in an integrated crop-livestock system (ICLS) to control gastrointestinal parasites. The experiment used 36 crossbred lambs (cross: Ile de France × White Dorper × Texel) divided into two groups. The WCS group was supplemented with whole cottonseed (WCS), and controls had no supplementation.